BIOAVAILABILITY OF LEAD IN SOIL SAMPLES
FROM THE NEW JERSEY ZINC NPL SITE
PALMERTON, PENNSYLVANIA
May 1996
College of Veterinary Medicine
University of Missouri-Columbia
OESGNBISICONSlJLWfTS
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BIOAVAILABILITY OF LEAD IN SOIL SAMPLES
FROM THE NEW JERSEY ZINC NPL SITE
PALMERTON, PENNSYLVANIA
May 1996
Stan W. Casteel, DVM, PhD, DABVT
Principal Investigator
Larry D. Brown, DVM, MPH
Margaret E. Dunsmore, BS
Co-Investigators
Veterinary Medical Diagnostic Laboratory
College of Veterinary Medicine
University of Missouri, Columbia
Columbia, Missouri
Christopher P. Weis, PhD, DABT
Gerry M. Henningsen, DVM, PhD, DABT/DABVT
Eva Hoffman, PhD
Study Design and Technical Advisors
US Environmental Protection Agency
Region VIII
Denver, Colorado
William J. Brattin, PhD
Tracy L. Hammon, MS
Technical Consultants
Roy F. Weston, Inc.
Denver, Colorado
Document Control Number 04800-030-0159
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ACKNOWLEDGEMENTS
The work described in this report is the product of a team effort involving a number of
people. In particular, the authors would like to acknowledge the efforts and support of the
following:
Dr. John Drexler at the University of Colorado, Boulder, performed the electron microprobe
and particle size analyses of the test materials.
Dr. Dan Paschal at the Centers for Disease Control and Prevention (CDCP) provided samples
of blood for use as internal quality control samples, and also performed independent
preparation and analyses of blood lead samples from the study for interlaboratory
comparisons.
Mr. Stan Christensen of the USEPA has provided oversight and quality assurance support
regarding many aspects of the analytical phases of this study.
Tamarac Medical performed the analyses of all of the samples generated during this study,
including blood, liver, kidney, bone, feed, water, and miscellaneous other materials.
Ms. Regina Prevosto at Roy F. Weston provided quality assurance oversight and review, and
assisted in development of data organization and analysis protocols.
Mr. Gerald Almquist at Roy F. Weston provided overall program management for the
project, including management of subcontractors and coordination of interactions between
team members.
Ross P. Cowart, DVM, MS, DACVIM, University of Missouri, Columbia, provided expert
evaluation of the health of the animals on study
James R. Turk, DVM, PhD, DACVP, University of Missouri, Columbia, performed
necropsy and pathological examination of all animals
John T. Payne, DVM, MS, DACVS, University of Missouri, Columbia, performed the
surgery to implant intravenous catheters and vascular access ports
Steven L. Stockhaim, DVM, MS, DACVP, University of Columbia, Missouri, assessed
clinical pathology data.
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EXECUTIVE SUMMARY
A study using young swine as test animals was performed to measure the gastrointestinal
absorption of lead from two soil samples from the New Jersey Zinc Superfund site located in
Palmerton, Pennsylvania. Young swine were selected for use in the study primarily because
the gastrointestinal physiology and overall size of young swine are similar to that of young
children, who are the population of prime concern for exposure to soil lead.
The two test soils were composites from different areas of the site. The first sample
contained 3,230 ppm lead, and was referred to as the "Location 2" sample. The second
sample contained 2,150 ppm lead, and was referred to as the "Location 4" sample. Groups
of 5 swine were given average oral doses of 7.7, 23.2, or 69.7 mg/kg-d of Location 2 soil or
11.6, 34.9, or 104.7 mg/kg-d of Location 4 soil for 15 days. This corresponded to target
average doses of 25, 75, or 225 ug/kg/day of lead. Other groups of animals were given a
standard lead reference material (lead acetate) either orally at doses of 0, 25, or 75 ug Pb/kg-
day, or intravenously at a dose of 100 ug Pb/kg-day. The amount of lead absorbed by each
animal was evaluated by measuring the amount of lead in the blood (measured on days -4, 0,
1, 2, 3, 5, 7, 9, 12, and 15), and the amount of lead in liver, kidney and bone (measured on
day 15 at study termination). The amount of lead present in blood or tissues of animals
exposed to test soils was compared to that for animals exposed to lead acetate, and the results
were expressed as relative bioavailability (RBA). For example, a relative bioavailability of
50% means that 50% of the lead in soil was absorbed equally as well as lead from lead
acetate, and 50% behaved as if it were not available for absorption. Thus, if lead acetate
were 40% absorbed, the test material would be 20% absorbed.
The RBA results for the two samples from the Palmerton site are summarized below:
Measurement
Endpoint
Blood Lead AUC
Liver Lead
Kidney Lead
Bone Lead
Test Material
Location 2
0.74
0.50
0.42
0.47
Location 4
0.58
0.54
0.34
0.39
Because the estimates of RBA based on blood, liver, kidney, and bone do not agree in all
cases, judgment must be used in interpreting the data. In general, we recommend greatest
emphasis be placed on the RBA estimates derived from the blood lead data. This is because
blood lead data are more robust and less susceptible to random errors than the tissue lead
data, so there is greater confidence in RBA estimates based on blood lead. In addition,
absorption into the central compartment is an early indicator of lead exposure, is the most
relevant index of central nervous system exposure, and is the standard measurement endpoint
ES-1
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in investigations of this sort. However, data from the tissue endpoints (liver, kidney, bone)
also provide valuable information. We consider the plausible range to extend from the RBA
based on blood AUC to the mean of the other three tissues (liver, kidney, bone). The
preferred range is the interval from the RBA based on blood to the mean of the blood RBA
and the tissue mean RBA. Our suggested point estimate is the mid-point of the preferred
range. These values are presented below:
Relative
Unavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Location 2
0.74-0.46
0.74-0.60
0.67
Location 4
0.58-0.42
0.58-0.50
0.54
These RBA estimates may be used to help assess lead risk at this site by refining the estimate
of absolute bioavailability (ABA) of lead in soil, as follows:
ABAsojl = ABAsoluble-RBAsoil
Available data indicate that fully soluble forms of lead are about 50% absorbed by a child.
Thus, the estimated absolute bioavailability of lead in the HL Smelter, LL Yard, and HL
Mill soils are as follows:
Absolute
Bioavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Location 2
37% -23%
37% -30%
34%
Location 4
29% -21%
29% -25%
27%
These absolute bioavailability estimates are appropriate for use in EPA's IEUBK model for
this site, although it is clear that there is both natural variability and uncertainty associated
with these estimates. This variability and uncertainty arises from several sources, including :
1) the inherent variability in the responses of different individual animals to lead exposure, 2)
uncertainty in the relative accuracy and applicability of the different measurement endpoints,
3) the extrapolation of measured RBA values in swine to young children, and 4) the potential
effect of food in the stomach on lead absorption. Thus, the values reported above are judged
to be reasonable estimates of typical lead absorption by children at this site, but should be
interpreted with the understanding that the values are not certain.
ES-2
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TABLE OF CONTENTS
1.0 INTRODUCTION 1
2.0 STUDY DESIGN 3
2.1 Test Materials 3
2.2 Experimental Animals 8
2.3 Diet 8
2.4 Dosing 10
2.5 Collection of Biological Samples 13
2.6 Preparation of Biological Samples for Analysis 13
2.7 Lead Analysis 14
3.0 DATA ANALYSIS 15
3.1 Overview 15
3.2 Fitting the Curves 15
3.3 Responses Below Quantitation Limits 16
3.4 Quality Assurance 16
4.0 RESULTS 21
4.1 Blood Lead vs. Time 21
4.2 Dose-Response Patterns 21
4.3 Calculated RBA Values 27
4.4 Estimated Absolute Bioavailability in Children 28
4.5 Uncertainty 29
5.0 REFERENCES 30
APPENDIX TITLE
A DETAILED DATA REVIEW
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TABLE
2-1
2-2
2-3
2-4
LIST OF TABLES
TITLE
PAGE
Metal Analysis of Test Materials 4
Geochemical Characteristics of Test Materials 6
Composition of Animal Diet 11
Dosing Protocol 12
LIST OF FIGURES
FIGURE
2-1
2-2
2-3
3-1
3-2
4-1
4-2
4-3
4-4
4-5
TITLE
PAGE
Lead Minerals Observed in Test Soils 5
Lead Particle Size Distribution 7
Body Weights of Test Animals 9
Comparison of Duplicate Analyses 18
Analysis of CDCP Check Samples 19
Blood Lead vs. Day 22
Blood Lead Dose-Response 23
Bone Lead Dose-Response 24
Liver Lead Dose-Response 25
Kidney Lead Dose-Response 26
11
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BIOAVAILABILITY OF LEAD IN SOIL SAMPLES
FROM NEW JERSEY ZINC SITE
PALMERTON, PENNSYLVANIA
1.0 INTRODUCTION
Absolute and Relative Bioavailabilitv
Bioavailability is a concept that relates to the absorption of chemicals and how absorption
depends upon the physical-chemical properties of the chemical and its medium (e.g., dust, soil,
rock, food, water, etc.) and the physiology of the exposed receptor. Bioavailability is normally
described as the fraction (or percentage) of a chemical which enters into the blood following an
exposure of some specified amount, duration and route (usually oral). In some cases,
bioavailability may be measured using chemical levels in peripheral tissues such as liver, kidney,
and bone, rather than blood. The fraction or percentage absorbed may be expressed either in
absolute terms (absolute bioavailability, ABA) or in relative terms (relative bioavailability,
RBA). Absolute bioavailability is measured by comparing the amount of chemical entering the
blood (or other tissue) following oral exposure to test material with the amount entering the
blood (or other tissue) following intravenous exposure to an equal amount of some dissolved
form of the chemical. Similarly, relative bioavailability is measured by comparing oral
absorption of test material to oral absorption of some fully soluble form of the chemical (e.g.,
either the chemical dissolved in water, or a solid form that is expected to fully dissolve in the
stomach). For example, if 100 ug of dissolved lead were administered in drinking water and
a total of 50 ug entered the blood, the ABA would be 0.50 (50%). Likewise, if 100 ug of lead
in soil were administered and 30 ug entered the blood, the ABA for soil would be 0.30 (30%).
If the lead dissolved in water were used as the reference substance for describing the relative
amount of lead absorbed from soil, the RBA would be 0.30/0.50 = 0.60 (60%). These values
(50% absolute bioavailability of dissolved lead and 30% absolute absorption of lead in soil) are
the values currently employed as defaults in EPA's IEUBK model.
It is important to recognize that simple solubility of a test material in water or some other fluid
(e.g., a weak acid intended to mimic the gastric contents of a child) may not be a reliable
estimator of bioavailability due to the non-equilibrium nature of the dissolution and transport
processes that occur in the gastrointestinal tract (Mushak 1991). For example, fluid volume and
pH are likely to be changing as a function of time, and transport of lead across the gut will
prevent an approach to equilibrium concentrations, especially for poorly soluble lead compounds.
However, information on the solubility of lead in different materials is useful in interpreting the
importance of solubility as a determinant of bioavailability. To avoid confusion, the term
"bioaccessability" is used to refer to the relative amount of lead that dissolves under a specified
set of test conditions.
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For additional discussion about the concept and application of bioavailability see Goodman et
al. (1990), Klaassen et al. (1996), and/or Gibaldi and Perrier (1982).
Using Bioavailability Data to Improve Exposure Calculations for Lead
Data on bioavailability are important for evaluating exposure and potential health effects for a
variety of different types of chemicals. This investigation focused mainly on evaluating the
bioavailability of lead in various samples of soil or other solid materials from mining, milling
or smelting sites. This is because lead may exist, at least in part, as poorly water soluble
minerals (e.g., galena), and may also exist inside particles of inert matrix such as rock or slag
of variable size, shape and association. These chemical and physical properties may tend to
influence (usually decrease) the solubility (bioaccessability) and the absorption (bioavailability)
of lead when ingested.
When data are available on the bioavailability of lead in soil, dust, or other soil-like waste
material at a site, this information can often be used to improve the accuracy of exposure and
risk calculations at that site. The basic equation for estimating the site-specific RBA of a test
soil is as follows:
i = ABASO|Uble • RBAsoii
where:
ABAsoil = Absolute bioavailability of lead in soil ingested by a child
ABAsolub,e = Absolute bioavailability in children of some dissolved or fully soluble
form of lead
RBAsoi, = RBA for soil measured in swine
Based on available information on lead absorption in humans and animals, the EPA estimates
that the absolute bioavailability of lead from water and other fully soluble forms of lead is
usually about 50% in children. Thus, when a reliable site-specific RBA value for soil is
available, it may be used to estimate a site-specific absolute bioavailability as follows:
ABAsoi, = 50%-RBAsoil
In the absence of site-specific data, the absolute absorption of lead from soil, dust and other
similar media is estimated by EPA to be about 30%. Thus, the default RBA used by EPA for
lead in soil and dust compared to lead in water is 30% 750% =60%. When the measured RBA
in soil or dust at a site is found to be less than 60% compared to some fully soluble form of
lead, it may be concluded that exposures to and risks from lead in these media at that site are
probably lower than typical default assumptions. If the measured RBA is higher than 60%,
absorption of and risk from lead in these media may be higher than usually assumed.
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2.0 STUDY DESIGN
A standardized study protocol for measuring absolute and relative bioavailability of lead was
developed based upon previous study designs and investigations that characterized the young pig
model (Weis et al. 1995). The study was performed as nearly as possible within the spirit and
guidelines of Good Laboratory Practices (GLP: 40 CFR 792). Standard Operating Procedures
(SOPs) that included detailed methods for all aspects of the study were prepared, approved, and
distributed to all study members prior to the study. The generalized study design, quality
assurance project plan and all standard operating procedures are documented in a project
notebook that is available through the administrative record.
2.1 Test Materials
Soil samples were collected from four different locations at the Palmerton site. Each sample was
a composite of four subsamples collected from four 1-foot square areas covering a 2-foot by 2-
foot area at each sampling location. The depth of the soil collected was 1 to 2 inches. All
samples consisted of dry, dusty leaf debris and organic soil. After initial screening, USEPA
Region III selected two of the four samples for analysis in the swine bioavailability assay. These
were referred to as "Location 2" and "Location 4". Both samples were sieved, and only the fine
fraction (particles less than about 250 um in diameter) derived from each sample were evaluated.
This is because it is believed that soil particles less than about 250 um are most likely to adhere
to the hands and be ingested by hand-to-mouth contact, especially in young children.
Table 2-1 lists the metal content of these samples measured using standard EPA Contract
Laboratory program (CLP) methods. Inspection of the data in this table reveals that although
the two test materials are similar in some regards, they do differ in the content of some
important constituents (e.g., barium, calcium, lead, sodium, and zinc). These data suggest that
these two samples are distinct, but it is beyond the scope of this project to attempt to identify
the sources of lead and other metals in the soil samples.
Each soil was well mixed and samples were analyzed by electron microprobe in order to identify
a) how frequently particles of various lead minerals were observed, b) how frequently different
types of mineral particles occur entirely inside particles of rock or slag ("included") and how
often they occur partially or entirely outside rock or slag particles ("liberated"), c) the size
distribution of particles of each mineral class, and d) approximately how much of the total
amount of lead in the sample occurs in each mineral type. This is referred to as "relative lead
mass". The results are summarized in Figure 2-1 and in Table 2-2.
As seen in Figure 2-1, the most common form of lead in each soil sample, both in terms of
particle frequency and relative lead mass, is manganese lead oxide. Most of the lead-bearing
particles are small, with mean lengths of different mineral classes typically ranging from about
5-30 um (Table 2-2). The distribution of particles sizes for each sample is presented graphically
in Figure 2.2. As noted above, small particles are often assumed to be more likely to adhere
to the hands and be ingested and/or be transported into the house. Further, small
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TABLE 2-1 METAL ANALYSIS OF TEST MATERIALS
Chemical
Aluminum
Antimony
Arsenic
Barium
Beryllium
Cadmium
Calcium
Chromium
Cobalt
Copper
Iron
Lead
Magnesium
Manganese
Mercury
Nickel
Potassium
Selenium
Silver
Sodium
Thallium
Vanadium
Zinc
Concentration (ppm)
Location 2
7750
6.0
110
6850
1.4
195
1160
30.2
18.8
462
25900
3230
725
6320
1.7
15.0
515
11.8
9.5
667
1.9
53.1
6500
Location 4
7850
7.4
134
1090
2.0
319
2480
26.6
17.4
350
26700
2150
684
9230
1.1
26.8
512
6.9
5.1
2100
0.85
49.8
19100
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FIGURE 2-1 LEAD MINERALS OBSERVED IN SITE SOILS
Fe-Pb Sulfate
Zn-Pb Silicate
PbSiO4
PbMO
Mn-Pb Oxide
he-ro uxiae
Lead Barite
F
yffifffy&S&fK&Sa
aitfrnna
'anel A: 1
m
.ocation 2
mmmwfWBi
I
HFreq
n Mass
Anglesite
Clays
0%
20%
40%
60%
80%
100%
Fe-Pb Sulfate
Zn-Pb Silicate
Lead Phosphate
Lead Vanidate
PbSiO4
PbMO
Mn-Pb Oxide
Fe-Pb Oxide
Lead Barite
Anglesite
Clays
0%
Panel B: Location 4
20%
40%
60%
80%
100%
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TABLE 2-2 GEOCHEMICAL CHARACTERISTICS OF TEST MATERIALS3
Mineral Form
Clays
Anglesite (PbSO4)
Lead barite
Fe-Pb Oxide
Mn-Pb Oxide
Pb-Metal Oxide
Pb-Silicate
Lead Vanidate
Lead Phosphate
Zn-Pb Silicate
Fe-Pb Sulfate
Location 2
Particle Freq.(%)
Count-
Based"
0.9%
1.8%
9.6%
13.2%
59.6%
-
--
-
14.0%
--
0.9%
Length-
Weighted'
0.6%
0.4%
5.0%
7.4%
68.8%
-
-
-
17.4%
-
0.5%
Particle Size* (um)
min
10
3
1
3
2
-
--
-
1
-
8
max
10
4
41
20
100
-
-
-
45
-
8
mean
10
4
8
8
17
-
-
-
19
-
8
Relative
Lead
Mass ' (%)
0.03%
6.0%
1.4%
1.5%
66.1%
ND
ND
ND
24.4%
ND
0.6%
Location 4
Particle Freq. (%)
Count-
Based
2.6%
6.8%
0.9%
12.0%
55.6%
14.5%
0.9%
4.3%
0.9%
1.7%
-
Length-
Weighted
2.9%
0.3%
0.5%
9.0%
80.8%
0.7%
0.2%
3.0%
0.6%
2.1%
-
Particle size (um)
min
8
1
12
8
4
1
4
5
15
12
-
max
45
1
12
40
110
1
4
35
15
40
--
mean
24
1
12
16
31
1
4
15
15
26
--
Relative
Lead Mass
(%)
0.1%
4.0%
0.1%
1.6%
65.8%
7.0%
1.4%
17.7%
0.7%
1.6%
ND
* Samples were analyzed using an electron microprobe (JEOL 8600) to identify the number of particles of each lead species present in each sample and the particle size (largest
dimension) of each particle.
b Percentage of all lead-bearing particles of the mineral form shown
c Percentage of total length of all lead particles consisting of mineral form shown
a Based on longest dimension of each particle
' Rough estimate of the percent of the total mass of lead present in each mineral form
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FIGURE 2-2 PARTICLE SIZE DISTRIBUTION
<5
Panel A: Location 2
10-19 2CM9 50-99 100-149 150-199 200-249
Particle Size (urn)
>250
Panel B: Location 4
20-49 50-99 100-149 150-199 200-249
Particle Size (urn)
>250
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particles have larger surface area-to-volume ratios than larger particles, and so may tend to
dissolve more rapidly in the acidic contents of the stomach than larger particles. Thus, small
particles (e.g., less than 25-50 um) are thought to be of greater potential concern to humans than
larger particles (e.g., 100-250 um or larger).
All of the lead-bearing particles in the sample from Location 2 and most (about 79%) of the
particles from Location 4 are "liberated" (i.e., they have some or all of their surface exposed
to the outside). This is of potential importance because liberated grains are thought to be more
likely to be solubilized by acidic fluids in the stomach that are grains that are entirely confined
within a glassy or rocky matrix.
2.2 Experimental Animals
Young swine were selected for use in these studies because they are considered to be a good
physiological model for gastrointestinal absorption in children (Weis and LaVelle 1991). The
animals were intact males of the Pig Improvement Corporation (PIC) genetically defined Line
26, and were purchased from Chinn Farms, Clarence, MO. The animals were held under
quarantine to observe their health for one week before beginning exposure to test materials. To
minimize weight variations between animals and groups, the number of animals purchased from
the supplier was six more than needed for the study, and the six animals most different in body
weight on day -4 (either heavier or lighter) were excluded from further study. The remaining
animals were assigned to dose groups at random. When exposure began (day zero), the animals
were about 5-6 weeks old (juveniles, weaned at 3 weeks) and weighed an average of about 14.6
kg. Animals were weighed every three days during the course of the study. The group mean
body weights over the course of the study are shown in Figure 2-3. On average, animals gained
about 0.6 kg/day, and the rate of weight gain was comparable in all groups.
All animals were housed in individual lead-free stainless steel cages. Each animal was examined
by a certified veterinary clinician (swine specialist) prior to being placed on study, and all
animals were examined daily by an attending veterinarian while on study. Blood samples were
collected for clinical chemistry and hematological analysis on days -4, 7, and 15 to assist in
clinical health assessments. In this study, there were no animals that were judged by the
principal investigator and the veterinary clinician to be seriously ill, and no animals were
removed from the study due to concerns over poor health.
2.3 Diet
Animals provided by the supplier were weaned onto standard pig chow purchased from MFA
Inc., Columbia, MO. In order to minimize lead exposure from the diet, the animals were
gradually transitioned from the MFA feed to a special low-lead feed (guaranteed less than 0.2
ppm lead, purchased from Zeigler Brothers, Inc., Gardners, PA) over the time interval from day
-7 to day -3, and this feed was then maintained for the duration of the study. The feed was
nutritionally complete and met all requirements of the National Institutes of Health-National
Research Council. The typical nutritional components and chemical analysis of the feed is
8
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FIGURE 2-3 BODY WEIGHTS OF TEST ANIMALS
O)
O)
0)
O)
2
4)
Study Day
— • — Grp1
--•••• Grp 6
— • — Grp 2
1 Grp 7
— A — Grp 3
Grp 8
• X • -Grp4
Grp 9
- - X-- -GrpS
— • — Grp 10
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presented in Table 2-3. Typically, the feed contained approximately 5.7% moisture, 1.7% fiber,
and provided about 3.4 kcal of metabolizable energy per gram. Periodic analysis of feed
samples during this program indicated the mean lead level (treating non-detects at one-half the
quantitation limit of 0.05 ppm) was less than 0.05 ppm.
Each day every animal was given an amount of feed equal to 5 % of the mean body weight of
all animals on study. Feed was administered in two equal portions of 2.5% of the mean body
weight at each feeding. Feed was provided at 11:00 AM and 5:00 PM daily. Drinking water
was provided ad libitum via self-activated watering nozzles within each cage. Periodic analysis
of samples from randomly selected drinking water nozzles indicated the mean lead concentration
(treating non-detects at one-half the quantitation limit) was less than 2 ug/L.
2.4 Dosing
The protocol for exposing animals to lead is shown in Table 2-4. The dose levels for lead
acetate were based on experience from previous investigations that showed that doses of 25-75
ug Pb/kg/day gave clear and measurable increases in lead levels in all endpoints measured
(blood, liver, kidney, bone). The doses of test materials were set at the same level as lead
acetate, with one higher dose (225 ug Pb/kg-day) included in case the test materials were found
to yield very low responses.
Animals were exposed to lead acetate or test material for 15 days, with the dose for each day
being administered in two equal portions given at 9:00 AM and 3:00 PM (two hours before
feeding). Doses were based on measured group mean body weights, and were adjusted every
three days to account for animal growth. For animals exposed by the oral route, dose material
was placed in the center of a small portion (about 5 grams) of moistened feed, and this was
administered to the animals by hand. Most animals consumed the dose promptly, but
occasionally some animals delayed ingestion of the dose for up to two hours (the time the daily
feed portion was provided). These delays are noted in the data provided in Appendix A, but are
not considered to be a significant source of error. Occasionally, some animals did not consume
some or all of the dose (usually because the dose dropped from their mouth while chewing).
All missed doses were recorded and the time-weighted average dose calculation for each animal
was adjusted downward accordingly.
For animals exposed by intravenous injection, doses were given via a vascular access port (VAP)
attached to an indwelling venous catheter that had been surgically implanted according to
standard operating procedures by a board-certified veterinary surgeon through the external
jugular vein to the cranial vena cava about 3 to 5 days before exposure began.
Actual mean doses, calculated from the administered doses and the measured body weights, are
also shown in Table 2-4.
10
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TABLE 2-3 TYPICAL FEED COMPOSITION2
Nutrient Name
Protein
Arginine
Lysine
Methionine
Met+Cys
Tryptophan
Histidine
Leucine
Isoleucine
Phenylalanine
Phe+Tyr
Threonine
Valine
Fat
Saturated Fat
Unsaturated Fat
Linoleic 18:2:6
Linoleic 18:3:3
Crude Fiber
Ash
Calcium
Phos Total
Available Phosphorous
Sodium
Potassium
Amount
20.1021%
1.2070%
1.4690%
0.8370%
0.5876%
0.2770%
0.5580%
1.8160%
1.1310%
1.1050%
2.0500%
0.8200%
1.1910%
4.4440%
0.5590%
3.7410%
1.9350%
0.0430%
3.8035%
4.3347%
0.8675%
0.7736%
0.7005%
0.2448%
0.3733%
Nutrient Name
Chlorine
Magnesium
Sulfur
Manganese
Zinc
Iron
Copper
Cobalt
Iodine
Selenium
Nitrogen Free Extract
Vitamin A
Vitamin D3
Vitamin E
Vitamin K
Thiamine
Riboflavin
Niacin
Pantothenic Acid
Choline
Pyridoxine
Folacin
Biotin
Vitamin B12
Amount
0.1911%
0.0533%
0.0339%
20.4719 ppm
118.0608 ppm
135.3710 ppm
8.1062 ppm
0.01 10 ppm
0.2075 ppm
0.3196 ppm
60.2340%
5.1892kIU/kg
0.6486 klU/kg
87.2080 lU/kg
0.9089 ppm
9.1681 ppm
10.2290 ppm
30.1147 ppm
19.1250 ppm
1019.8600 ppm
8.2302 ppm
2.0476 ppm
0.2038 ppm
23.4416 ppm
a Nutritional values provided by Zeigler Bros., Inc.
11
-------
TABLE 2-4 DOSING PROTOCOL
Group
1
2
3
4
5
6
7
8
9
10
Number
of
Animals
7
5
5
5
5
5
5
5
5
5
Dose
Material
Administered
Lead Acetate
None
Lead Acetate
Lead Acetate
Location 2 soil
Location 2 soil
Location 2 soil
Location 4 soil
Location 4 soil
Location 4 soil
Exposure
Route
Intravenous
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Lead Dose (ug Pb/kg-d)
Target
100
0
25
75
25
75
225
25
75
225
Actual3
106
0
24.9
74.7
25.1
74.9
226
25.2
74.9
224
Doses were administered in two equal portions given at 9:00 AM and 3:00 PM each
day. Doses were based on the mean weight of the animals in each group, and were
adjusted every three days to account for weight gain.
Calculated as the administered daily dose divided by the measured or extrapolated
daily body weight, averaged over days 0-14 for each animal and each group.
12
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2.5 Collection of Biological Samples
Blood
Samples of blood were collected from each animal four days before exposure began (day -4),
on the first day of exposure (day 0), and on days 1, 2, 3, 5, 7, 9, 12, and 15 following the start
of exposure. All blood samples were collected by vena-puncture of the anterior vena cava, and
samples were immediately placed in purple-top Vacutainer® tubes containing EDTA as
anticoagulant. Blood samples were collected each sampling day beginning at 8:00 AM,
approximately one hour before the first of the two daily exposures to lead on the sampling day
and 17 hours after the last lead exposure the previous day. This blood collection time was
selected because the rate of change in blood lead resulting from the preceding exposures is
expected to be relatively small after this interval (LaVelle et al. 1991, Weis et al. 1993), so the
exact timing of sample collection relative to last dosing is not likely to be critical.
Following collection of the final blood sample at 8:00 AM on day 15, all animals were humanely
euthanized and samples of liver, kidney and bone (the right femur) were removed and stored in
lead-free plastic bags for lead analysis. Samples of all biological samples collected were
archived in order to allow for reanalysis and verification of lead levels, if needed, and possibly
for future analysis for other metals (arsenic, cadmium, etc.). All animals were also subjected
to detailed examination at necropsy by a certified veterinary pathologist in order to assess overall
animal health.
2.6 Preparation of Biological Samples for Analysis
Blood
One mL of whole blood was removed from the purple-top Vacutainer and added to 9.0 mL of
"matrix modifier", a solution recommended by the Centers for Disease Control and Prevention
(CDCP) for analysis of blood samples for lead. The composition of matrix modifier is 0.2%
(v/v) ultrapure nitric acid, 0.5% (v/v) Triton X-100, and 0.2% (w/v) dibasic ammonium
phosphate in deionized and ultrafiltered water. Samples of the matrix modifier were routinely
analyzed for lead to ensure the absence of lead contamination.
Liver and Kidney
One gram of soft tissue (liver or kidney) was placed in a lead-free screw-cap teflon container
with 2 mL of concentrated (70%) nitric acid and heated in an oven to 90°C overnight. After
cooling, the digestate was transferred to a clean lead-free 10 mL volumetric flask and diluted
to volume with deionized and ultrafiltered water.
13
-------
Bone
The right femur of each animal was removed and defleshed, and dried at 100°C overnight. The
dried bones were then placed in a muffle furnace and dry-ashed at 450°C for 48 hours.
Following dry ashing, the bone was ground to a fine powder using a lead-free mortar and pestle,
and 200 mg was removed and dissolved in 10.0 mL of 1:1 (v:v) concentrated nitric acid/water.
After the powdered bone was dissolved and mixed, 1.0 mL of the acid solution was removed
and diluted to 10.0 mL by addition of 0.1% (w/v) lanthanum oxide (La2O3) m deionized and
ultrafiltered water.
2.7 Lead Analysis
Samples of biological tissue (blood, liver, kidney, bone) and other materials (food, water,
reagents and solutions, etc.) were arranged in a random sequence and provided to EPA's
analytical laboratory in a blind fashion (identified to the laboratory only by a chain of custody
tag number). Each sample was analyzed for lead using a Perkin Elmer Model 5100 graphite
furnace atomic absorption spectrophotometer. Internal quality assurance samples were run every
tenth sample, and the instrument was recalibrated every 15th sample. A blank, duplicate and
spiked sample were run every 20th sample.
All results from the analytical laboratory were reported in units of ug Pb/L of prepared sample.
The quantitation limit was defined as three-times the standard deviation of a set of seven
replicates of a low-lead sample (typically about 2-5 ug/L). The standard deviation was usually
about 0.3 ug/L, so the quantitation limit was usually about 0.9-1.0 ug/L (ppb). For prepared
blood samples (diluted 1/10), this corresponds to a quantitation limit of 10 ug/L (1 ug/dL). For
soft tissues (liver and kidney, diluted 1/10), this corresponds to a quantitation limit of 10 ug/kg
(ppb) wet weight, and for bone (final dilution = 1/500) the corresponding quantitation limit is
0.5 ug/g (ppm) ashed weight.
14
-------
3.0 DATA ANALYSIS
3.1 Overview
Studies on the absorption of lead are often complicated because some biological responses to lead
exposure may be non-linear functions of dose (i.e., tending to flatten out or plateau as dose
increases). The cause of this non-linearity is uncertain but might be due either to non-linear
absorption kinetics and/or to non-linear biological response per unit dose absorbed. When the
dose-response curve for either the reference material (lead acetate) and/or the test material is
non-linear, RBA is equal to the ratio of doses that produce equal responses (not the ratio of
responses at equal doses). This is based on the simple but biologically plausible assumption that
equal absorbed doses yield equal biological responses. Applying this assumption leads to the
following general methods for calculating RBA from a set of non-linear experimental data:
1. Plot the biological responses of individual animals exposed to a series of oral
doses of soluble lead (e.g., lead acetate). Fit an equation which gives a smooth
line through the observed data points.
2. Plot the biological responses of individual animals exposed to a series of doses
of test material. Fit an equation which gives a smooth line through the observed
data.
3. Using the best fit equations for reference material and test material, calculate
RBA as the ratios of doses of test material and reference material which yield
equal biological responses. Depending on the relative shape of the best-fit lines
through the lead acetate and test material dose response curves, RBA may either
be constant (dose-independent) or variable (dose-dependent).
The principal advantage of this approach is that it is not necessary to understand the basis for
a non-linear dose response curve (non-linear absorption and/or non-linear biological response)
in order to derive valid RBA estimates. Also, it is important to realize that this method is very
general, as it will yield correct results even if one or both of the dose-response curves are linear.
In the case where both curves are linear, RBA is dose-independent and is simply equal to the
ratio of the slopes of the best-fit linear equations.
3.2 Fitting the Curves
There are a number of different mathematical equations which can yield reasonable fits with the
dose-response data sets obtained in this study. Conceptually, any equation which gives a smooth
fit would be acceptable, since the main purpose is to allow for interpolation of responses
between test doses. In selecting which equations to employ, the following principles were
applied: 1) mathematically simple equations were preferred over mathematically complex
equations, 2) the shape of the curves had to be smooth and biologically realistic, without
inflection points, maxima or minima, and 3) the general form of the equations had to be able
15
-------
to fit data not only from this one study, but from all the studies that are part of this project.
After testing a wide variety of different equations, it was found that all data sets could be well
fitted using one of the following three forms:
Linear (LIN): Response = a + b-Dose
Exponential (EXP): Response = a + c-(l-exp(-d-Dose))
Combination (LIN+EXP): Response = a + b-Dose + c-(l-exp(-d-Dose))
Although underlying mechanism was not considered in selecting these equations, the linear
equation allows fitting data that do not show evidence of saturation in either uptake or response,
while the exponential and mixed equations allow evaluation of data that appear to reflect some
degree of saturation in uptake and/or response.
Each dose-response data set was fit to each of the equations above. If one equation yielded a
fit that was clearly superior (as judged by the value of the adjusted correlation coefficient R2)
to the others, that equation was selected. If two or more models fit the data approximately
equally well, then the simplest model (that with the fewest parameters) was selected. In the
process of finding the best-fits of these equations to the data, the values of the parameters (a,
b, c, and d) were subjected to some constraints, and some data points (those that were outside
the 95% prediction limits of the fit) were excluded. These constraints and outlier exclusion steps
are detailed in Appendix A (Section 3). In general, most blood lead AUC dose-response curves
were best fit by the exponential equation, and most dose-response curves for liver, kidney and
bone were best fit by linear equations.
3.3 Responses Below Quantitation Limit
In some cases, most or all of the responses in a group of animals were below the quantitation
limit for the endpoint being measured. For example, this was normally the case for blood lead
values in unexposed animals (both on day -4 and day 0, and in control animals), and also
occurred during the early days in the study for animals given test materials with low
bioavailability. In these cases, all animals which yielded responses below the quantitation limit
were evaluated as if they had responded at one-half the quantitation limit.
3.4 Quality Assurance
A number of steps were taken throughout this study and the other studies in this project to
ensure the quality of the results. These steps are summarized below.
16
-------
Duplicates
A randomly selected set of about 5 % of all samples generated during the study were submitted
to the laboratory in a blind fashion for duplicate analysis. The raw data are presented in
Appendix A, and Figure 3-1 plots the results for blood (Panel A, upper) and for bone, liver and
kidney (Panel B, lower). As seen, there was good intra-laboratory reproducibility between
duplicate samples for both blood and tissues, with linear regression lines having a slope near
1.0, an intercept near zero, and an R2 value near 1.0.
Standards
The Centers for Disease Control and Prevention (CDCP) provides a variety of blood lead "check
samples" for use in quality assurance programs for blood lead studies. Each time a group of
blood samples was prepared and sent to the laboratory for analysis, several CDCP check samples
of different concentrations were included in random order and in a blind fashion.
The results for the samples submitted during this study are presented in Appendix A, and the
values are plotted in Figure 3-2 (Panel A, upper). As seen, the analytical results obtained for
the check samples tended to be low for the "low" and "medium" standards employed (nominal
concentrations =1.7 ug/dL and 4.8 ug/dL). Although there was some scatter in the results for
the "high" check sample, the mean of all results (14.5 ug/dL) is close to the nominal value of
this standard (14.9 ug/dL).
Interlaboratory Comparison
An interlaboratory comparison of blood lead analytical results was performed by sending a set
of 20 randomly selected whole blood samples from this study to CDCP for blind independent
preparation and analysis. The results are presented in Appendix A, and the values are plotted
in Figure 3-2 (Panel B, lower). As seen, the values obtained by EPA tended to be slightly lower
(about 15%) than the values reported by CDCP. The reason for this apparent discrepancy
between the EPA laboratory and the CDCP laboratory is not clear, but might be related to
differences in sample preparation techniques. Regardless of the reason, the differences are
sufficiently small that they are likely to have no significant effect on calculated RBA values.
In particular, it is important to realize that if both the lead acetate and test soils dose-response
curves are biased by the same factor, then the biases cancel in the calculation of the ratio.
Data Audits and Spreadsheet Validation
All analytical data generated by EPA's analytical laboratory were validated prior to being
released in the form of a database file. These electronic data files were "decoded" (linking the
sample tag to the correct animal and day) using Microsoft's database system ACCESS® (Version
5 for Windows). To ensure that no errors occurred in this process, original electronic files were
printed out and compared to printouts of the tag assignments and the decoded data.
17
-------
FIGURE 3-1 COMPARISON OF DUPLICATE ANALYSES
PALMERTON
Panel A
Blood Lead
y = 0.97x + 0.016
R2 = 0.99
8 10 12
Duplicate Value (ug/dL)
160
140 -
~ 120
3. 100 •
80
01
3
IB
C
'5
§
40
20 |
0
Panel B
Tissue Lead
•=1.06x-7.02
R2 = 0.98
20
40
60 80
Duplicate Value (ug/L)
100
120
140
18
-------
FIGURE 3-2 CDCP CHECK SAMPLES FOR PALMERTON NPL SITE
00
0.
PANEL A
1fl
4 C
12 •
9 •
6 •
• 3 2 3 !
• BDL '
I - I 0
5 -3 -1
ANALYSIS OF CDCP BLOOD LEAD CHECK SAMPLES FO
PALMERTON
A 16.1 * 165
A 153
A wV3'4 A 12 9
I 3.? *i 4.0 • 4.3 »«* 1*5 -41
' 1 ^ 10 • BDL » BDL
1 3 5 7 9 11 13 15
Study Day
R
• Low Std
• Med Std
A High Std
Low Std
- " - Med Std
High Std
6.0
-.5.0
_i
5
3.4.0
PANEL B INTERLABORATORY COMPARISON BETWEEN EPA AND CDCP
FOR PALMERTON
Theoretical
y-1.00x+0.00
0.8068X + 0.4229
R2 = 0.8902
2.0 3.0 4.0
CDCP PbB Results (ug/dL)
-------
All spreadsheets used to manipulate the data and to perform calculations (see Appendix A) were
validated by hand-checking random cells for accuracy.
20
-------
4.0 RESULTS
The following sections provide results based on the group means for each dose group
investigated in this study. Appendix A provides detailed data for each individual animal.
Results from this study will be compared and contrasted with the results from other studies in
a subsequent report.
4.1 Blood Lead vs Time
Figure 4-1 shows the group mean blood lead values as a function of time during the study. As
seen, blood lead values began at or below quantitation limits (about 1 ug/dL) in all groups, and
remained at or below quantitation limits in control animals (Group 2). In animals given repeated
oral doses of lead acetate (Groups 3 and 4), Location 2 soil (Groups 5-7, upper panel), or
Location 4 soil (Groups 8-10, lower panel), blood levels began to rise within 1-2 days, and
tended to plateau by the end of the study (day 15). A similar pattern was observed in animals
exposed to lead acetate by intravenous injection (Group 1).
4.2 Dose-Response Patterns
Blood Lead
The measurement endpoint used to quantify the blood lead response was the area under the curve
(AUC) for blood lead vs time (days 0-15). AUC was selected because it is the standard
pharmacokinetic index of chemical uptake into the blood compartment, and is relatively
insensitive to small variations in blood lead level by day. The AUC was calculated using the
trapezoidal rule to estimate the AUC between each time point that a blood lead value was
measured (days 0, 1,2, 3, 5, 7, 9, 12, and 15), and summing the areas across all time intervals
in the study. The detailed data and calculations are presented in Appendix A, and the results
are shown graphically in Figure 4-2. Each data point reflects the group mean exposure and
group mean response, with the variability in dose and response shown by standard error bars.
The figure also shows the best-fit equation through each data set.
As seen, the dose response pattern is non-linear for both the soluble reference material (lead
acetate, abbreviated "PbAc"), and for each of the two test soils. Dose response curves for soil
from both Location 2 and Location 4 are lower than those seen for lead acetate, with Location
4 being the lowest.
Tissue Lead
The dose-response data for lead levels in bone, liver and kidney (measured at sacrifice on day
15) are detailed in Appendix A, and are shown graphically in Figures 4-3 through 4-5,
respectively.
21
-------
FIGURE 4-1 GROUP MEAN BLOOD LEAD BY DAY FOR
NEW JERSEY ZINC NPL SITE, PALMERTON, PA
I
m
.o
o.
-2
16
14
12
10
8
6
4
Panel A
Palmerton Location 2 Soil
**
* " 1 IV
E " 2 Control
A - 3 PbAc (25)
X - 4 PbAc (75)
5 Location 2 (25)
6 Location 2 (75)
7 Location 2 (225)
468
Study Day
10 12 14
16
I
CO
CL
Panel B
Palmerton Location 4 Soil
• * - 1 iv
—D—2 Control
~ A ~ 3 PbAc (25)
« X - 4 PbAc (76)
Q 8 Location 4 (25)
9 Location 4 (75)
*> 10 Location 4 (225)
22
-------
OJ
FIGURE 4-2 BLOOD LEAD DOSE-RESPONSE, GROUP MEANS ± SEMS FOR
NEW JERSEY ZINC NPL SITE, PALMERTON, PA
140
120
!£, ioo
re
T3
I
5
^i
S 80
O
13
T3
ra
0)
-1 60
T3
O
O
00
40
20
<
0
0
A
rVOffscale
Mean Dose = 1 06 +/- 3
Mean Resp = 226 +/- {
— ]
3
3
[BLOODAU
— - - —
1 ___
c
...... . . - -
\
. ... - ..
_._ — — ~~
Best Fit Eqn for Loc 2 Soil
y-7.22+104*(1-exp(-0.006X))
Best Fit Eqn for PbAc
y=7.22+104*(1-ex|
\
\
«/
r
D(-0.0081X)) J
S^ H H
\
\
^"""
....-.--•
r
/
/
/
/
Best Fit Eqn for Loc 4 Soil
y=7.22+ 1 04*(1 -exp(-0.0047X))
, -i r^
' i-' "..".--
1, . • ir^ 1
Measu
r
i
......
ed Data Points
• Avg PbAc
B Avg Loc2
A Avg Loc4
50 100 150 200 250 3CX
Lead Dose (ug Pb/kg-d)
-------
ro
12
FIGURE 4-3 BONE LEAD DOSE-RESPONSE, GROUP MEANS ± SEMS FOR
NEW JERSEY ZINC NPL SITE, PALMERTON, PA
10
IV Offscale
Mean Dose = 106+7- 33
Mean Resp = 46 +/- 23
M
W
-"
TJ
to
IV
c
o
m
BONE
Best Fit Eqn for Loc 2 Soil
y=0.87+0.030X
Best Fit Eqn for PbAc
y=0.87+0.063X
Best Fit Eqn for Loc 4 Soil
y=0.87+0.025X
Measurec
Data Points
• Avg PbAc
B Avg Loc2
A Avg Loc4
100 150
Lead Dose (ug Pb/kg-d)
200
250
300
-------
400
350
300
250
FIGURE 4-4 LIVER LEAD DOSE-RESPONSE, GROUP MEANS ± SEMS FOR
NEW JERSEY ZINC NPL SITE, PALMERTON, PA
IV Offscale
Mean Dose = 106+/-33
MeanResp = 1517+/- 187
-
I
O)
•o
«
0>
Eqn for PbAc F
150
100
50
LIVER
Best Fit Eqn for Loc 4 Soil
y=18.4+1.10X
Best Fit Eqn for Loc 2 Soil
y=18.4+1.01X
Measured Data Points
• Avg PbAc
• Avg Loc2
A Avg Loc4
50
100
150
200
250
300
Lead Dose (ug Pb/kg-d)
-------
NJ
ON
FIGURE 4-5 KIDNEY LEAD DOSE-RESPONSE, GROUP MEANS ± SEMS FOR
NEW JERSEY ZINC NPL SITE, PALMERTON, PA
01
n
w
>.
0)
c
TJ
OCTl
-arm
250
OfV\
1Cfi
100
en
i
n
A
IV Offscale
Mean Dose = 106+/-33
Mean Resp = 1 336 +/-
Best Fit
115
Ean for Pt
3Ac
y=25.1+2.14X
" " A
£
/
l
/
S \
^
I
! '
/
^*^
^
/
-
H
A
/
H
^-fi
^ .-•
J
/
/
M
H -
^-
^^
j
KIDNEY
- --jBest Fit Eqn for Loc 2 Soil
|y=25.1+2.14X
1
/
c^'^T-
_ * /
^
•
^"'
Best Fit Eqn for Loc 4 Soil
y=25.1+0.725X
>
^^
\^
a 1
F
. •** j
Me
^
, '
- ~
, •""
isured Data Points
• Avg PbAc
B Avg Loc2
A Avg Loc 4
50
100
150
200
250
300
Lead Dose (ug Pb/kg-d)
-------
As seen, all of these dose response curves for tissues are fit by linear equations. The responses
of the two test soils tend to be generally similar to each other, and the responses for each of the
three tissues (liver, bone and kidney) all appear to be lower than for lead acetate.
4.3 Calculated RBA Values
Relative bioavailability values were calculated for each test material for each measurement
endpoint (blood, bone, liver, kidney) using the method described in Section 3.0. The results are
shown below:
Measurement
Endpoint
Blood Lead AUC
Liver Lead
Kidney Lead
Bone Lead
Test material
Location 2
0.74
0.50
0.42
0.47
Location 4
0.58
0.39
0.54
0.34
Recommended RBA Values
As shown above, for each test material, there are four independent estimates of RBA (based on
blood, liver, kidney, and bone), and the values do not agree in all cases. In general, we
recommend greatest emphasis be placed on the RBA estimates derived from the blood lead data.
There are several reasons for this recommendation, including the following:
1) Blood lead calculations are based on multiple measurements over time, and so are
statistically more robust than the single measurements available for tissue
concentrations. Further, blood is a homogeneous medium, and is easier to
sample than complex tissues such as liver, kidney and bone. Consequently, the
AUC endpoint is less susceptible to random measurement errors, and RBA values
calculated from AUC data are less uncertain.
2. Blood is the central compartment and one of the first compartments to be affected
by absorbed lead. In contrast, uptake of lead into peripheral compartments (liver,
kidney, bone) depend on transfer from blood to the tissue, and may be subject to
a variety of toxicokinetic factors that could make bioavailability determinations
more complicated.
3. The dose-response curve for blood lead is non-linear, similar to the non-linear
dose-response curve observed in children (e.g., see Sherlock and Quinn 1986).
Thus, the response of this endpoint is known to behave similarly in swine as in
children, and it is not known if the same is true for the tissue endpoints.
27
-------
4. Blood lead is the classical measurement endpoint for evaluating exposure and
health effects in humans, and the health effects of lead are believed to be
proportional to blood lead levels.
However, data from the tissue endpoints (liver, kidney, bone) also provide valuable information.
We consider the plausible range to extend from the RBA based on blood AUC to the mean of
the other three tissues (liver, kidney, bone). The preferred range is the interval from the RBA
based on blood to the mean of the blood RBA and the tissue mean RBA. Our suggested point
estimate is the mid-point of the preferred range. These values are presented below:
Relative
Bioavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Location 2
0.74-0.46
0.74-0.60
0.67
Location 4
0.58-0.42
0.58-0.50
0.54
4.4 Estimated Absolute Bioavailability in Children
These RBA estimates may be used to help assess lead risk at this site by refining the estimate
of absolute bioavailability (ABA) of lead in soil, as follows:
ABAsnll = ABA
vsoil
•soluble
RBA
soil
Available data indicate that fully soluble forms of lead are about 50% absorbed by a child
(USEPA 1991, 1994). Thus, the estimated absolute bioavailability of lead in site soils are
calculated as follows:
ABALocatjon 2 = 50% •RBALocation2
ABALocation4 = 50%-RBALocation4
Based on the RBA values shown above, the estimated absolute bioavailabilities in children are
as follows:
Absolute
Bioavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Location 2
37% -23%
37% -30%
34%
Location 4
29% -21%
29% -25%
27%
28
-------
4.5 Uncertainty
These absolute bioavailability estimates are appropriate for use in EPA's IEUBK model for this
site, although it is clear that there is both variability and uncertainty associated with these
estimates. This variability and uncertainty arises from several sources. First, differences in
physiological and pharmacokinetic parameters between individual animals leads to variability in
response even when exposure is the same. Because of this inter-animal variability in the
responses of different animals to lead exposure, there is mathematical uncertainty in the best fit
dose-response curves for both lead acetate and test material. This in turn leads to uncertainty
in the calculated values of RBA, because these are derived from the two best-fit equations.
Second, there is uncertainty in how to weight the RBA values based on the different endpoints,
and how to select a point estimate for RBA that is applicable to typical site-specific exposure
levels. Third, there is uncertainty in the extrapolation of measured RBA values in swine to
young children. Even though the immature swine is believed to be a useful and meaningful
animal model for gastrointestinal absorption in children, it is possible that differences in stomach
pH, stomach emptying time, and other physiological parameters may exist and that RBA values
in swine may not be precisely equal to values in children. Finally, studies in humans reveal that
lead absorption is not constant even within an individual, but varies as a function of many
factors (mineral intake, health status, etc.). One factor that may be of special importance is time
after the last meal, with the presence of food tending to reduce lead absorption. The values of
RBA measured in this study are intended to estimate the maximum uptake that occurs when lead
is ingested in the absence of food. Thus, these values may be somewhat conservative for
children who ingest lead along with food. The magnitude of this bias is not known, although
preliminary studies in swine suggest the factor may be relatively minor.
29
-------
5.0 REFERENCES
Gibaldi, M. and Perrier, D. 1982. Pharmacokinetics (2nd edition) pp 294-297. Marcel Dekker,
Inc, NY, NY.
Goodman, A.G., Rail, T.W., Nies, A.S., and Taylor, P. 1990. The Pharmacological Basis
of Therapeutics (8th ed.) pp. 5-21. Pergamon Press, Inc. Elmsford, NY.
Klaassen, C.D., Amdur, M.O., and Doull, J. (eds). 1996. Cassarett andDoull's Toxicology:
The Basic Science of Poisons, pp. 190. McGraw-Hill, Inc. NY,NY
LaVelle, J.M., Poppenga, R.H., Thacker, B.J., Giesy, J.P., Weis, C., Othoudt R, and
Vandervoot C. 1991. Unavailability of Lead in Mining Waste: An Oral Intubation Study in
Young Swine. In: The Proceedings of the International Symposium on the Bioavailability and
Dietary Uptake of Lead. Science and Technology Letters 3:105-111.
Mushak, P. 1991. Gastro-intestinal Absorption of Lead in Children and Adults: Overview of
Biological and Biophysico-chemical Aspects. In: The Proceedings of the International
Symposium on the Bioavailability and Dietary Uptake of Lead. Science and Technology Letters
3:87-104.
Sherlock, J.C., and Quinn, M.J. 1986. Relationship Between Blood Lead Concentration and
Dietary Intake in Infants: the Glasgow Duplicate Diet Study 1979-1980. Food Additives and
Contaminants 3:167-176.
USEPA 1991. Technical Support Document on Lead. United States Environmental Protection
Agency, Environmental Criteria and Assessment Office. ECAO-CIN-757.
USEPA 1994. Guidance Manual for the Integrated Exposure Uptake Biokinetic Model for Lead
in Children. United States Environmental Protection Agency, Office of Emergency and
Remedial Response. Publication Number 9285.7-15-1. EPA/540/R-93/081.
Weis, C.P. and LaVelle, J.M. 1991. Characteristics to consider when choosing an animal
model for the study of lead bioavailability. In: The Proceedings of the International Symposium
on the Bioavailability and Dietary Uptake of Lead. Science and Technology Letters 3:113-119.
Weis, C.P., Henningsen, G.M., Poppenga, R.H., and Thacker, B.J. 1993. Pharmacokinetics
of Lead in Blood of Immature Swine Following Acute Oral and Intravenous Exposure. The
Toxicologist 13(1): 175.
Weis, C.P., Poppenga, R.H., Thacker, B.J., Henningsen, G.M., and Curtis, A. 1995.
"Design of Pharmacokinetic and Bioavailability Studies of Lead in an Immature Swine
30
-------
Model." In: LEAD IN PAINT. SOIL. AND DUST: HEALTH RISKS. EXPOSURE
STUDIES. CONTROL MEASURES. MEASUREMENT METHODS. AND QUALITY
ASSURANCE. ASTM STP 1226. Michael E. Beard and S. D. Allen Iske, Eds., American
Society for Testing and Materials, Philadelphia, 1995.
31
-------
APPENDIX A
DETAILED DATA AND CALCULATIONS FOR
USEPA SWINE BIOAVAILABILITY STUDY
PHASE II, EXPERIMENT 9
NEW JERSEY ZINC NPL SITE
PALMERTON, PA
-------
APPENDIX A
DETAILED DATA SUMMARY
1.0 OVERVIEW
Performance of this study involved collection and reduction of a large number of data items.
All of these data items and all of the data reduction steps are contained in a Microsoft Excel
spreadsheet named "PALMERTN.XLS" that is available upon request from the administrative
record. This file is intended to allow detailed review and evaluation by outside parties of all
aspects of the study.
The following sections of this Appendix present printouts of selected tables and graphs from the
XLS file. These tables and graphs provide a more detailed documentation of the individual
animal data and the data reduction steps performed in this study than was presented in the main
text. Any additional details of interest to a reader can be found in the XLS spreadsheet.
2.0 RAW DATA AND DATA REDUCTION STEPS
2.1 Body Weights and Dose Calculations
Animals were weighed on day -1 (one day before exposure) and every three days thereafter
during the course of the study. Doses of lead for the three days following each weighing were
based on the group mean body weight, adjusted by addition of 1 kg to account for the expected
weight gain over the interval. After completion of the experiment, body weights were estimated
by interpolation for those days when measurements were not collected, and the actual
administered doses (ug Pb/kg) were calculated for each day and then averaged across all days.
If an animal missed a dose or was given an incorrect dose, the calculation of average dose
corrected for these factors. These data and data reduction steps are shown in Tables A-l and
A-2. Doses which required adjustment are shown by a heavy black box outlining the value in
Table A-l.
2.2 Blood Lead vs Time
Blood lead values were measured in each animal on days -4, 0, 1, 2, 3, 5, 7, 9, 12, and 15.
The raw laboratory data (reported as ug/L of diluted blood) are shown in Table A-3. These data
were adjusted as follows: a) non-detects were evaluated by assuming a value equal to one-half
the quantitation limit, and b) the concentrations in diluted blood were converted to units of ug/dL
in whole blood by dividing by a factor of 1 dL of blood per L of diluted sample. The results
are shown in the right-hand column of Table A-3. Figures A-l to A-3 plot the results for
individual animals organized by group and by day. Figure A-4 plots the mean for each dosing
group by day.
A-l
-------
After adjustment as above, values that were more than a factor of 1.5 above or below the group
mean for any given day were "flagged" by computer as potential outliers. These values are
shown in Table A-4 by cells that are shaded gray. Each data point identified in this way was
reviewed and professional judgment was used to decide if the value should be retained or
excluded. In order to avoid inappropriate biases, blood lead outlier designations were restricted
to values that were clearly aberrant from a time-course and/or dose-response perspective. In this
study, none of the flagged values were excluded (Table A-5).
2.3 Blood Lead AUC
The area under the blood lead vs time curve for each animal was calculated by finding the area
under the curve for each time step using the trapezoidal rule:
AUC(d; to dj) = 0.5*(ri+rj)*(dj-di)
where:
d = day number
r = response (blood lead value) on day i (r) or day j (rj)
The areas were then summed for each of the time intervals to yield the final AUC for each
animal. These calculations are shown in Table A-6. If a blood lead value was missing (either
because of problems with sample preparation, or because the measured value was excluded as
an outlier), the blood lead value for that day was estimated by linear interpolation.
2.4 Liver, Kidney and Bone Lead Data
At sacrifice (day 15), samples of liver, kidney and bone (femur) were removed and analyzed for
lead. The raw data (expressed as ug Pb/L of prepared sample) are summarized in Table A-7.
These data were adjusted as follows: a) non-detects were evaluated by assuming a value equal
to one-half the quantitation limit, and b) the concentrations in prepared sample were converted
to units of concentration in the original biological sample by dividing by the following factors:
Liver: 0.1 kg wet weight/L prepared sample
Kidney: 0.1 kg wet weight/L prepared sample
Bone: 2 gm ashed weight/L prepared sample
The resulting values are shown in the right-hand column of Table A-7.
A-2
-------
3.0 CURVE FITTING
Basic Equations
A commercial curve-fitting program (Table Curve-2D™ Version 2.0 for Windows, available
from Jandel Scientific) was used to derive best fit equations for each of the individual dose-
response data sets derived above. A least squares regression method was used for both linear
and non-linear equations. As discussed in the text, three different user-defined equations were
fit to each data set:
Linear (LIN): Response = a + b-Dose
Exponential (EXP): Response = a + c-(l-exp(-d-Dose))
Combination (LIN+EXP): Response = a + b-Dose + c-(l-exp(-d-Dose))
Constraints
In the process of finding the best-fits of these equations to the data, the values of the parameters
(a, b, c, and d) were constrained as follows:
• Parameter "a" (the intercept, equal to the baseline or control value of the
measurement endpoint) was constrained to be non-negative and was forced in all
cases to be the same for the reference material (lead acetate) and the test
materials. This is because, by definition, all dose-response curves for groups of
animals exposed to different materials must arise from the same value at zero
dose. In addition, for blood lead data, "a" was constrained to be equal to the
mean of the control group ±20% (typically 7.5 ± 1.5 AUC units).
• Parameter "b" (the slope of the linear dose-response line) was constrained to non-
negative values, since all of the measurement endpoints evaluated are observed
to increase, not decrease, as a function of lead exposure.
• Parameter "c" (the plateau value of the exponential curve) was constrained to be
non-negative, and was forced to be the same for the reference material (lead
acetate) and the test material. This is because: 1) it is expected on theoretical
grounds that the plateau (saturation level) should be the same regardless of the
source of lead, and 2) curve-fitting of individual curves tended to yield values of
"c" that were close to each other and were not statistically different.
• Parameter "d" (which determines where the "bend" in the exponential equation
occurs) was constrained to be greater than 0.0045 for the lead acetate blood lead
(AUC) dose-response curve. This constraint was judged to be necessary because
A-3
-------
the weight of evidence from all studies clearly showed the lead acetate blood lead
dose response curve was non-linear and was best fit by an exponential equation,
but in some studies there were only two low doses of lead acetate used to define
the dose-response curve, and this narrow range data set could sometimes be fit
nearly as well by a linear as an exponential curve. The choice of the constraint
on "d" was selected to be slightly lower than the observed best-fit value of "d"
(0.006) when data from all lead acetate AUC dose-response curves from all of the
different studies in this program were used. This approach may tend to
underestimate relative bioavailability slightly in some studies (especially at low
dose), but use of the information gained from all studies is judged to be more
robust than basing fits solely on the data from one study.
In general, one of these models (the linear, the exponential, or the combination) usually yielded
a fit (as judged by the value of the adjusted correlation coefficient R2 and by visual inspection
of the fit of the line through the measured data points) that was clearly superior to the others.
If two or more models fit the data approximately equally well, then the simplest model (that with
the fewest parameters) was selected.
Outlier Identification
During the dose-response curve fitting process, all data were carefully reviewed to identify any
anomalous values. Typically, the process used to identify outliers was as follows:
Step 1 Any data points judged to be outliers based on information derived from analysis
of data across multiple studies (as opposed to conclusions drawn from within the
study) were excluded.
Step 2 The remaining raw data points were fit to the equation judged to be the most
likely to be the best fit (linear, exponential, or mixed). Table Curve 2-D was
then used to plot the 95% prediction limits around the best fit line. All data
points that fell outside the 95% prediction limits were considered to be outliers
and were excluded.
Step 3 After excluding these points (if any), a new best-fit was obtained. In some cases,
data points originally inside the 95% prediction limits were now outside the
limits. However, further iterative cycles of data point exclusion were not
performed, and the fit was considered final.
It should be noted that professional judgment can be imposed during any stage of the above
outlier identification process. In this study, one additional data point was determined to be an
outlier and excluded from analysis.
A-4
-------
Curve Fit Results
Table A-8 lists the data used to fit these curves, indicating which endpoints were excluded as
outliers and why. Table A-9 shows the type of equation selected to fit each data set, and the
best fit parameters. The resulting best-fit equations for the data sets are shown in Figures A-5
to A-16. Values excluded as outliers are represented in the figures by the symbol " + ".
4.0 RESULTS -- CALCULATED RBA VALUES
The value of RBA for a test substance was calculated for a series of doses using the following
procedure:
1. For each dose, calculate the expected response to test material, using the best fit
equation through the dose-response data for that material.
2. For each expected response to test material, calculate the dose of lead acetate that
is expected to yield an equivalent response. This is done by "inverting" the dose-
response curve for lead acetate, solving for the dose that corresponds to a
specified response.
3. Calculate RBA at that dose as the ratio of the dose of lead acetate to the dose of
test material. For the situation where both curves are linear, the value of RBA
is the ratio of the slopes (the "b" parameters). In the case where both curves are
exponential and where both curves have the same values for parameters "a" and
"c", the value of RBA is equal to the ratio of the "d" parameters.
The results are summarized in Table A-10.
5.0 QUALITY ASSURANCE DATA
A number of steps were taken throughout this study and the other studies in this project to
ensure the quality of the results, including 5% duplicates, 5% standards, a program of
interlaboratory comparison. These steps are detailed below.
Duplicates
Duplicate samples were prepared and analyzed for about 5 % of all samples generated during the
study. Table A-ll lists the first and second values for blood, liver, kidney, and bone. The
results are shown in Figure 3-1 in the main text.
Standards
The Centers for Disease Control and Prevention (CDCP) provides a variety of blood lead "check
samples" for use in quality assurance programs for blood lead studies. Each time a group of
A-5
-------
blood samples was prepared and sent to the laboratory for analysis, several CDCP check samples
of different concentrations were included. Table A-12 lists the concentrations reported by the
laboratory compared to the nominal concentrations indicated by CDCP for the samples submitted
during this study, and the results are plotted in Figure 3-2 in the main text.
Interlaboratory Comparison
An interlaboratory comparison of blood lead analytical results was performed by sending a set
of 15 randomly selected whole blood samples from this study to CDCP for independent analysis.
The data are presented in Table A-13, and the results are plotted in Figure 3-3 in the main text.
A-6
-------
Swi» Study Ptui. II Exp 9 PiknMon
TABLE A-1 BODY WEIGHTS AND ADMINISTERED DOSES, BY DAY
Body weights were measured on days -1, 2, 5, 8, 11, 14. Weights for other days are estimated, based on linear interpolation between measured values.
Group IDt
1 907
1 912
1 919
1 930
1 942
1 943
1 953
2 901
2 902
2 920
2 925
2 928
3 905
3 909
3 927
3 931
3 940
4 923
4 933
4 948
4 950
4 956
5 911
5 929
5 934
5 947
5 954
6 903
6 910
6 938
6 951
6 955
7 906
7 908
7 916
7 918
7 922
8 913
8 914
8 932
8 937
8 946
9 924
9 926
9 944
9 949
9 957
10 917
10 921
10 939
10 941
10 945
Day-1
BW (kg) ug Pb/day
1156 00
14.8 0.0
12.82 00
1252 00
1406 00
1514 00
1358 00
1508 00
1626 00
1592 00
169 00
14 1 0.0
1678 0.0
1472 0.0
1448 0.0
1276 00
1334 00
11 14 00
14 16 00
144 00
1456 00
1326 00
1256 00
1228 0.0
1538 00
14.24 00
1376 00
163 00
159 00
1434 00
1452 00
15 14 00
1546 0.0
1352 00
1284 0.0
1322 00
1552 0.0
1132 00
126 00
146 00
1404 00
1 1 94 00
1368 00
117 00
1478 00
143 00
139 0.0
12 16 00
1486 0.0
1636 0.0
147 00
1272 00
DayO
BW (kg) ug Pb/day
12.1 1449.7
15.3 1449.7
13.3 1449.7
13.1 1449.7
14.5 1449.7
15.7 1449.7
14.2 1449.7
153 0.0
16.6 00
165 00
174 00
145 00
17.3 385.4
15.2 | 289.1
15.0 385.4
13.2 385.4
137 385.4
114 10878
146 1087.8
149 1087.8
15 1 1087.8
13.6 1087.8
130 366.1
12.9 3661
157 366.1
147 366.1
141 3661
168 1218.0
163 1218.0
145 12180
149 1218.0
157 12180
15.9 3400.2
13.7 :::S34QO;5!;S:
13.3 3400.2
13.5 3400.2
16.0 3400.2
114 347.5
131 347.5
149 3475
146 347.5
125 347.5
142 11004
12.2 11004
155 11004
144 1100.4
142 11004
124 34110
14.8 | 1705.5
16.8 3411.0
151 34110
13.2 3411.0
Day1
BW (kc|) ug Pb/day
126 1449.7
15.7 14497
137 1449.7
13.6 14497
150 1449.7
162 14497
148 1449.7
156 0.0
17.0 0.0
170 00
178 00
149 00
17.9 385.4
15.7 385.4
15.5 385.4
13.7 3854
142 3854
116 10878
151 1087.8
154 10878
15.7 10878
13.8 1087 8
13.3 3661
135 3661
161 3661
15.2 366.1
145 3661
17.3 121B.O
167 1218.0
147 12180
15.2 12180
163 12180
164 3400.2
13.9 3400.2
13.7 3400.2
13.8 3400.2
16.4 3400.2
115 3475
135 347.5
15 1 347 5
152 3475
13 1 347 5
147 11004
12.6 11004
161 11004
145 1100.4
144 11004
12.7 3411.0
148 3411.0
173 3411.0
156 3411.0
136 3411.0
Day 2
BW (kg) ug Pb/day
13.12 1449.7
16.22 1449.7
14.2 1449.7
1412 1449.7
15.46 14497
16.76 14497
15.42 1449.7
15.86 0.0
17.42 0.0
17.52 0.0
18.32 0.0
15.32 0.0
1846 385.4
16.22 385.4
16.02 385.4
14.2 385.4
1456 385.4
11.8 10878
15.58 1087.8
1594 1087.8
16.3 1087.8
14 14 1087.8
1374 366.1
1404 366.1
164 366.1
15.62 366.1
1486 3661
1778 1218.0
1706 12180
1482 12180
15.56 1218.0
1694 1218.0
1686 3400.2
1412 3400.2
1418 3400.2
14.16 3400.2
16.82 3400.2
11.58 347.5
14.02 347.5
1542 3475
158 347.5
1362 3475
15.28 1100.4
1308 1100.4
16.82 1100.4
1462 1100.4
14.68 11004
12.92 34110
14.7 34110
17.72 3411.0
16.02 3411.0
14.08 3411.0
Day3
BW (kg) ug Pb/day
137 1604.3
16.8 1604.3
14.6 1604.3
14.6 1604.3
161 1604.3
17.3 1604.3
159 16043
167 0.0
18.3 00
183 0.0
187 0.0
15.6 00
18.9 422.3
167 422.3
16.5 422.3
150 422.3
150 422.3
12.3 1181
16.2 1181
16.3 1181.
16.8 1181.
14.7 1181
14.2 398.3
145 398.3
16.7 398.3
16.3 398.3
154 398.3
18.3 1307.4
17.8 13074
15.4 13074
160 13074
17.5 13074
172 3651.3
143 3651.3
145 3651.3
145 3651.3
172 3651.3
119 377.2
14.5 377.2
16.1 377.2
16.3 377.2
14.1 377.2
15.9 1192.2
136 1192.2
17.2 1192.2
152 1192.2
152 1192.2
13.3 3619.8
15.3 3619.8
18.2 3619.8
16.8 3619.8
14.6 3619.8
Day 4
BW (kg) ug Pb/day
14.3 1604.3
17.4 1604.3
14.9 16043
15.1 1604.3
16.8 16043
17.8 16043
16.3 16043
17.5 0.0
191 0.0
19.1 00
19.1 0.0
15.8 00
19.3 4223
17.3 4223
17.1 422.3
15.9 4223
155 422.3
129 11814
169 1181.4
166 1181.4
17.3 1181.4
153 1181.4
148 398.3
151 3983
170 398.3
170 398.3
159 3983
188 13074
186 13074
159 13074
164 13074
180 13074
17.5 36513
14 5 3651 3
148 36S1.3
149 3651.3
17.6 36513
12.2 3772
150 377.2
168 377.2
16 7 377.2
145 3772
164 11922
14.2 1192.2
177 1192.2
158 11922
157 11922
13.7 36198
15.9 36198
18.7 36198
17.5 36198
15.1 36198
Days
BW (kg) ug Pb/day
14 84 1604.3
17.94 16043
15,32 16043
15.62 1604.3
17 4 1604 3
1826 1604.3
168 16043
1834 00
1996 00
19.86 00
19.5 00
16.1 00
19.76 422.3
1778 4223
17.6 422.3
167 422.3
16.02 422.3
134 11814
1756 11814
1696 11814
17.82 11814
1584 11814
1526 3983
15 56 398 3
17.26 3983
17.7 3983
16.38 3983
19.38 13074
19.36 1307 4
1648 13074
1686 | 980.6
186 13074
1784 36513
1466 3651.3
15.08 36513
15.24 36513
18.02 36513
125 3772
15.56 3772
17.52 3772
17.16 377.2
14 92 377 2
17.02 11922
14.72 11922
18.1 11922
1632 11922
1618 11922
1402 3619.8
1648 36198
19.12 36198
1824 3619.8
15.56 3619.8
Day6
BW (kg) ug Pb/day
153 19043
183 1904 3
157 19043
162 19043
17 8 1904 3
189 19043
174 19043
189 00
206 00
20 1 00
20 1 00
168 00
203 464.3
185 4643
182 4643
17 1 464 3
16.5 464 3
14 1 12987
180 | 9740
175 12987
184 12987
165 12987
157 4358
16 2 435 8
17 8 435 8
184 4358
171 4358
20 1 1435.2
199 14352
168 14352
174 14352
193 14352
185 38628
155 38628
157 38628
159 38628
18.8 38628
13 1 413 3
160 4133
182 4133
177 4133
155 4133
177 13101
151 13101
189 13101
168 13101
16 9 1310 1
14 5 3978 9
170 39789
199 39789
188 39789
160 39789
Shaded boxes show days in which administered doses were ingested late
Days which required adjustment for missed or partially missed doses
DayO
Pig 909 * Dropped most of one doughball. Daily dose adjusted to 75%
Pig 921 - Did not eat one doughball Daily dose adjusted to 50%
Day 5
Day 6
Day 8
Day 9
Pig 951 - Ate 1/2 of one doughball, dropped the rest through cage bottom. Daily dose adjusted to 75%
Pig 933 - Vomit found after one dosing Daily dose adjusted to 75%
Pig 933 - Vomitted AM doughball Dose was treated as missed. Daily dose adjusted to 50%
Pig 946 - Possibly vomitted one dose. Daily dose adjusted to 75%
Pig 941 - Portion of one dose fell on floor Daily dose adjusted to 75%
Pig 945 - Portion of one dose fell on floor Daily dose adjusted to 75%
-------
TABLE A-1 (cont.)
Son Study Ph««« II Eap t Pibnnton
Day 7
BW (kg) ug Pb/day
157 1904.3
186 1904.3
160 1904.3
167 19043
18.3 19043
19.5 19043
18.0 1904.3
194 00
21 2 0.0
202 00
207 00
175 00
20 8 464 3
19 3 464 3
18 9 464 3
175 4643
17 1 464 3
148 12987
185 12987
180 12987
190 12987
17 1 1298 7
162 435.8
169 435.8
183 435.8
19 1 435 8
178 4358
209 14352
204 1435.2
172 14352
179 1435.2
200 14352
192 3862.8
162 38628
16.3 38628
165 38628
196 3862.8
137 413.3
164 4133
188 4133
182 4133
160 4133
18 4 1310 1
154 13101
197 13101
173 13101
177 13101
15.1 39789
175 39789
207 3978.9
194 39789
164 39789
Day 8
BW (kg) ug Pb/day
16 18 1904.3
19 1904.3
1638 1904.3
1728 19043
1872 1904.3
20 16 1904 3
18.58 1904.3
1996 00
2176 0.0
2044 00
2124 00
1818 00
2126 4643
20 04 464.3
195 4643
17 88 464 3
17 58 464 3
1544 12987
1898 | 6494
1858 12987
1962 1298.7
1772 12987
1662 4358
17 54 435 8
1882 435.8
1982 4358
185 4358
21 66 1435 2
2092 1435.2
1754 1435.2
1844 1435.2
2068 14352
1986 3862.8
17 04 3862 8
1694 38628
1718 38628
2042 38628
1424 4133
1684 4133
195 4133
1866 4133
1656 | 3100
1902 13101
1572 1310.1
2046 13101
1782 13101
1846 13101
156 3978.9
1798 39789
21 56 3978 9
1996 39789
1684 39789
Day 9
BW (kg) ug Pb/day
16.5 2084.6
19.6 2084.6
17.0 20846
181 20846
19.3 20846
209 20846
19.1 2084,6
20.3 00
224 00
210 00
21.9 00
185 00
21.8 506.3
206 506.3
20 2 506.3
186 506.3
182 506 3
16.2 1430.1
194 1430.1
19.1 14301
20.3 1430.1
187 1430.1
173 481.5
184 4815
19.1 481.5
20.3 4815
19.1 481.5
222 15636
216 1563.6
18 1 1563 6
190 1563.6
212 15636
203 43398
175 4339.8
176 4339.8
176 43398
21 1 4339.8
150 4540
173 4540
20.2 4540
193 4540
172 454.0
19 5 1447.2
16.2 1447.2
210 1447.2
183 1447.2
189 1447.2
15,9 4362.3
18 5 4362 3
22 1 4362.3
206 1 32717
17.3 | 32717
Day 10
BW(kg) ugPb/dai
16.8 2084.6
202 2084.6
17.6 2084.6
190 2084.6
19.9 2084.6
21.5 2084.6
19.7 2084.6
206 00
23.1 0.0
21 5 00
227 0.0
189 0.0
224 5063
21.1 506.3
20.8 506.3
19.3 506.3
187 506.3
16.9 1430.1
19.9 14301
19.6 1430.1
21.1 1430.1
196 1430.1
180 481.5
19.3 481.5
19.4 4815
20.8 481.5
19.7 481.5
22.7 1563.6
223 15636
187 15636
19.5 1563.6
218 1563.6
20.7 4339.8
18.0 43398
183 4339.8
179 43398
21.9 4339.8
158 4540
17.7 4540
21.0 454.0
199 454.0
17.8 454.0
200 14472
16.7 1447.2
21.6 1447.2
18.8 1447.2
194 1447.2
16.1 4362.3
18 9 4362.3
22.7 4362.3
211 4362.3
17 8 4362 3
Day 11
BW (kg) ug Pb/day
17.18 2084.6
20.82 2084.6
18.14 2084.6
19.82 2084.6
20.46 2084.6
2224 2084.6
2026 2084.6
20.92 0.0
23.78 0.0
22.1 0.0
2336 0.0
1928 00
2292 5063
2162 5063
2146 5063
19.98 506.3
19.3 506.3
17.64 1430.1
2032 1430.1
20.1 1430.1
2178 1430.1
20.58 14301
187 481.5
2016 481.5
1966 481.5
2132 481.5
2036 481.5
2316 15636
23.06 1563.6
19 3 1563.6
20.08 1563.6
22.32 15636
21.06 4339.8
1848 43398
1902 4339.8
1832 4339.8
226 43398
1658 454.0
18 16 454 0
21.74 454.0
20.52 454.0
1842 4540
2054 1447.2
17.14 1447.2
22.2 14472
19.24 1447.2
19.8 1447.2
1636 4362.3
194 43623
23.2 4362.3
2174 43623
183 43623
Day 12
BW (kg) ug Pb/day^
178 2305.1
21 3 2305.1
189 2305.1
207 23051
21.1 2305.1
23.0 2305.1
213 23051
221 0.0
24.6 00
23.0 0.0
24.2 00
20.3 0.0
23.8 551.4
22.4 551.4
222 5514
20.8 5514
198 5514
18.2 1581.3
20.6 15813
20.7 1581.3
223 15813
21 0 1581 3
187 526.0
20.4 526.0
19.9 526.0
21.7 526.0
21.1 526.0
23.9 1693.8
23.6 1693.8
200 16938
206 16938
230 1693.8
22.1 4701.6
193 4701.6
197 47016
18.8 47016
23.5 4701 6
17.1 5021
188 5021
223 502.1
21.1 502.1
19.2 502.1
21.3 15588
18.2 1558.8
23.2 1558.8
20.1 1558.8
20.6 1558.8
17.2 4680.0
20.2 46800
24 1 4680 0
22.5 4680.0
190 46800
Day 13
BW (kg) ug Pb/day
18.5 23051
218 23051
19.6 2305.1
215 2305.1
218 23051
23.8 23051
22.3 2305.1
233 0.0
255 00
23.9 00
25.0 00
21.3 00
24.7 5514
231 5514
23 0 551 4
21 6 551 4
20.3 551 4
18.8 15813
210 1581.3
213 15813
22.8 1581.3
21.4 1581 3
18.8 526.0
20.7 5260
20.2 526.0
22.1 526.0
21.8 5260
246 1693.8
24.1 16938
20 6 1693 8
21.2 16938
23.6 1693.6
230 4701.6
200 47016
204 47016
19.3 47016
243 47016
176 5021
19.5 5021
22.8 5021
21.7 5021
199 5021
22.0 15588
19.3 1558.8
242 15588
209 1558.8
21.3 15588
181 4680.0
210 46800
251 46800
23 2 4680 0
197 :¥4a8K6:y
Day 14
BW (kg) ug Pb/d y
19.12 2305
22.3 2305
2034 2305
2232 2305
22.5 2305
2452 2305
2326 2305
24.52 0.0
26 3 0 0
24 8 0.0
2588 0.0
223 00
25 64 551 4
23.82 5514
2376 5514
2236 5514
208 5514
19 32 1581 3
21 3 1581 3
2192 15813
23 24 1581 3
21 76 1581 3
1882 5260
20 98 526 0
20 42 526 0
22 42 526 0
22.5 5260
25 26 1693.8
2462 16938
21 28 1693 8
21 76 1693.8
24 3 1693 8
2404 4701.6
20 8 4701 6
21 04 4701 6
19.8 47016
25 16 4701 6
1808 502
2016 502
2332 502.
2222 502
2062 502
22 8 1558 8
20.38 1558.8
2526 15588
2178 15588
2208 1558.8
189 46800
2176 46800
26 04 4680 0
2392 46800
20 42 4680 0
Day 15
BW (kg) ug Pb/day
198 00
22 8 00
211 0.0
232 00
232 00
253 00
243 00
25 7 0.0
27 1 0.0
257 00
267 00
23.3 00
26 5 0.0
246 00
245 00
232 00
21 3 00
199 00
21 6 0.0
225 00
23.7 00
22 2 0 0
189 00
21 3 00
20.7 0 0
228 00
23.2 0.0
260 00
251 00
21 9 00
22 3 0.0
250 00
250 00
21 6 00
21 7 00
203 00
260 00
186 00
208 00
23.8 0.0
228 00
21 4 00
236 00
215 00
263 00
226 00
22 8 0 0
197 00
225 0.0
270 00
246 0.0
21 1 0.0
-------
TABLE A-2
Body Weight Adjusted Doses
(Dose for Day/BW for Day)
Swine Study Ptiast II Exp 9 Palmerton
Group
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
8
8
8
8
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
ID*
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
DayO
120009
94918
109165
111.061
99797
92456
102141
0000
0000
0000
0000
0000
22226
18991
25705
29109
28036
95757
74337
72941
71 849
80261
28263
28.453
23289
24905
25916
72529
74785
84000
81 928
77382
213491
247828
255911
251 246
213134
30465
26581
23364
23758
27800
77420
90493
71.177
76381
77712
274785
115185
202875
225297
258932
Day1
115057
92065
105511
106701
96691
89378
97910
0000
0000
0000
0000
0000
21 531
24.517
24854
28090
27230
93938
72008
70514
69198
78560
27430
27213
22796
24149
25260
70.459
73051
83083
80061
74.541
207414
244267
247587
245561
207498
30235
25652
22942
22842
26608
74620
87195
68 178
75820
76311
269289
231 202
197548
218935
250318
| Day 2
110497
89378
102093
102671
93772
86498
94.015
0000
0000
0000
0000
0000
20878
23.761
24057
27.141
26470
92186
69820
68243
66736
76.931
26645
26.075
22323
23438
24637
68504
71 395
82186
78278
71 901
201673
240807
239788
240.127
202.152
30009
24786
22536
21 994
25514
72016
84128
65422
75267
74959
264009
232 041
192494
212921
242259
Day 3
117.158
95531
110084
109732
99604
92948
101 026
0000
0000
0000
0000
0000
22352
25227
25522
28091
28066
95789
72746
72568
70294
80331
27957
27381
23869
24416
25920
71 391
73340
85043
81 747
74.737
212450
255336
252162
251 467
212038
31 733
25954
23400
23208
26841
75170
87490
69128
78503
78538
272439
236691
199036
215979
248385
| Day 4
112.450
92377
107 334
106104
95759
90331
98 182
0000
0000
0000
0000
0000
21 851
24467
24734
26616
27187
91 819
69905
71 083
68236
77.351
26997
26459
23466
23420
25092
69370
70316
82089
79590
72446
208487
252162
247043
245383
207225
30935
25069
22426
22578
26038
72518
84116
67458
75679
76033
265122
227851
194056
206846
240252
DayS
108106
89425
104718
102707
92200
87858
95493
0000
0000
0000
0000
0000
21 371
23751
23994
25287
26361
88164
67278
69658
66296
74583
26.101
25598
23076
22503
24316
67461
67531
79333
58158
70290
204669
249065
242129
239587
202625
30176
24242
21 530
21 981
25282
70047
80992
65867
73051
73684
258188
219648
189320
198454
232635
I Days
124572
104097
121 498
117742
106742
100791
109484
0000
0000
0000
0000
0000
22917
25052
25464
27163
28071
92237
54012
74211
70505
78868
27734
26868
24511
23676
25505
71 261
72193
85259
82546
74388
208650
249965
246038
243147
205250
31 598
25853
22734
23403
26722
74073
87031
69366
77889
77338
273 527
234329
199610
211 494
248889
Day 7
121 035
102125
118820
113847
104 173
97522
105872
0000
0000
0000
0000
0000
22365
24074
24610
26552
27216
87988
70175
71 990
68281
75977
26957
25818
23814
22801
24492
68670
70353
83507
80119
71 808
201 327
237760
236691
233637
196881
30256
25181
21 937
22759
25810
71 382
85145
66593
75641
74017
263969
227626
191 785
205239
242419
| Days
117694
100226
116257
110202
101 725
94459
102491
0000
0000
0000
0000
0000
21 839
23169
23810
25968
26411
84.113
34212
69898
66193
73290
26221
24.846
23.156
21 988
23557
66260
68604
81 824
77831
69400
194502
226690
228028
224843
189167
29024
24.543
21 195
22149
18.718
68880
83340
64032
73519
70.970
255058
221 296
184550
199.344
236277
DayS
126236
106320
122863
115000
108009
99963
108912
0000
0000
0000
0000
0.000
23211
24618
25122
27250
27890
88423
73615
74927
70310
76585
27811
26150
25209
23696
25.183
70560
72277
86260
82353
73662
214205
247705
246113
247 141
205224
30226
26273
22423
23548
26426
74114
89370
68783
79.111
76544
275166
236396
197330
159182
188826
| Day 10
123738
103129
118756
109868
104858
96747
105816
0000
0000
0000
0000
0000
22636
24003
24334
26260
27036
84588
71 961
72989
67906
72865
26740
24965
24845
23127
24392
69003
69970
83555
80048
71 813
210058
241 100
236802
241 906
198406
28734
25621
21 626
22814
25506
72240
86832
66938
77.115
74778
270838
230484
192568
206288
244890
Day 11
121 337
100124
114916
105175
101 885
93731
102891
0000
0000
0000
0000
0000
22090
23418
23593
25340
26233
81071
70379
71 149
65661
69490
25749
23884
24491
22584
23649
67513
67806
81 016
77869
70054
206068
234838
228170
236889
192027
27382
25000
20883
22125
24647
70458
84434
65189
75218
73091
266644
224861
188030
200658
238377
| Day 12
129309
108 155
122138
111 611
109042
100224
108426
0000
0000
0000
0000
0.000
23142
24667
24808
26544
27848
86885
76589
76367
71 016
75396
28068
25742
26414
24255
24960
70989
71 832
84860
82064
73708
213192
244197
238741
249908
200466
29397
26670
22549
23811
26215
73206
85554
67132
77604
75817
271 988
231 836
193816
208309
246229
Day 13
124782
105708
117569
107 282
105644
97018
103555
0000
0000
0000
0000
0000
22294
23884
23981
25567
27.163
84291
75396
74193
69498
74008
28009
25.402
26083
23851
24143
68966
70282
82144
79896
71 650
204003
234767
230848
243522
193428
28561
25758
22028
23188
25248
70705
80767
64307
74465
73114
259 232
223140
186504
201 782
237403
| Day 14
120562
103370
113331
103277
102451
94011
99103
0000
0000
0000
0000
0000
21 505
23149
23207
24660
26.510
81 848
74239
72140
68042
72670
27949
25071
25759
23461
23378
67055
68798
79596
77840
69704
195574
226038
223460
237455
186868
27771
24906
21 531
22597
24350
68368
76487
61 710
71.570
70598
247619
215074
179724
195652
229187
Avg Dose
11950
9913
11367
10887
101.49
9426
10235
000
000
000
000
000
2215
2378
2452
26.64
2718
8861
6844
72.19
6867
7581
2724
2600
2421
2348
2469
6933
7084
8292
7869
7250
20638
24217
23997
24212
20083
2977
2547
2221
2285
2545
7235
8489
6675
7579
7490
26586
22051
19262
20443
23902
Target Dose
8888888
o
0
0
0
o
25
25
25
25
26
75
75
75
7S
75
25
25
25
25
,...,, ,25,. .,. .„
75
75
75
75
75
225
225
225
225
22S
25
25
25
25
25
75
75
75
75
75
225
22S
225
225
225
% Target
120
99
114
109
101
94
102
89
95
96
107
109
118
91
96
92
101
109
104
97
94
99
92
94
111
105
97
92
108
107
108
89
119
102
89
91
102
96
113
89
101
100
118
98
86
91
106
Avg%
106
99
100
100
100
101
101
100
100
-------
SmK Stxly PIMM II Em » Prim«ton
TABLE A - 3 RAW AND ADJUSTED BLOOD LEAD DATA
pig number sample
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
8-990162
8-990165
8-990173
8-990125
8-990142
8-990176
8-990170
8-990143
8-990157
8-990140
8-990155
8-990137
8-990121
8-990131
8-990150
8-990136
8-990135
8-990156
8-990172
8-990132
8-990158
8-990153
8-990144
8-990126
8-990159
8-990128
8-990169
8-990164
8-990154
8-990168
8-990134
8-990123
8-990167
8-990163
8-990127
8-990129
8-990161
8-990124
8-990133
8-990146
8-990166
8-990122
8-990120
8-990152
8-990148
8-990149
8-990130
8-990141
8-990147
8-990175
8-990171
8-990138
8-990226
8-990189
8-990183
8-990204
8-990177
8-990211
8-990230
8-990197
8-990180
8-990220
8-990229
8-990178
8-990184
8-990203
8-990196
8-990200
8-990201
8-990221
8-990224
8-990210
8-990195
8-990205
8-990232
B-990222
8-990212
8-990186
8-990209
8-990225
8-990228
8-990199
8-990193
8-990215
8-990219
group
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
material administered dosage qualifier
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
100 <
100 <
100 <
100 <
100 <
100 <
100 <
0 <
0 <
0 <
0 <
0 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
225 <
225 <
225 <
225 <
225 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
225 <
225 <
225 <
225 <
225 <
100 <
100 <
100 <
100 <
100 <
100
100 <
0 <
0 <
0 <
0 <
0 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
25 <
25 <
25 <
25 <
25 <
75 <
75
75 <
75 <
75 <
225
lab result (ug/L) day
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
13
1
1
1
1
1
1
1
1
1 2
1.3
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
-4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
source file
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
MATRIX Adjusted Value (ug/dL)'
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
SLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
SLOOD
BLOOO
BLOOO
BLOOO
SLOOD
BLOOO
BLOOO
BLOOO
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
SLOOD
BLOOD
BLOOO
05
05
0.5
0.5
0.5
0.5
05
05
05
05
05
05
05
0.5
05
0.5
0.5
0.5
05
05
05
05
05
05
0.5
05
0.5
0.5
0.5
05
05
05
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
05
05
0.5
05
0.5
0.5
05
05
0.5
0.5
05
05
0.5
05
0.5
1.3
0.5
0.5
0.5
0.5
0.5
05
0.5
05
0.5
0.5
0.5
0.5
05
05
05
0.5
05
05
0.5
05
0.5
05
1.2
0.5
05
05
13
-------
Sxiiw Sbdy Phut II Exp 9 Ptfnwtofl
pig number
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
•ample
8-990213
8-990191
8-990185
8-990208
8-990192
8-990227
8-990214
8-990216
8-990202
8-990179
8-990188
8-990182
8-990181
8-990231
8-990218
8-990217
8-990190
8-990207
8-990198
8-990262
8-990279
8-990246
8-990236
8-990289
8-990247
8-990241
8-990265
8-990275
8-990258
8-990271
8-990235
8-990276
8-990277
8-990244
8-990255
8-990240
8-990284
8-990287
8-990285
8-990290
8-990252
8-990260
8-990257
8-990270
8-990239
8-990281
8-990269
8-990238
8-990251
8-990256
8-990243
8-990248
8-990254
8-990266
8-990261
8-990250
8-990267
8-990274
8-990263
8-990234
8-990283
8-990288
8-990242
8-990264
8-990273
8-990268
8-990280
8-990249
8-990282
8-990286
8-990259
8-990326
8-990294
8-990344
8-990329
8-990305
8-990306
8-990318
8-990299
8-990331
8-990298
8-990315
8-990314
8-990335
8-990301
8-990333
8-990317
8-990296
group
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
2
2
2
2
2
3
3
3
3
3
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
material administered
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
dosage qualifier
225
225
225
225
25 <
25
25 <
25
25 <
75 <
75 <
75 <
75 <
75 <
225 <
225 <
225 <
225 <
225 <
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25 <
25 <
25
25
25 <
75 <
75
75
75 <
75
25
25 <
25 <
25
25 <
75 <
75
75 <
75
75
225
225
225
225
225
25 <
25 <
25 <
25 <
25 <
75
75
75
75
75 <
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25 <
25
25 <
25
25
lab result (ug/L)
1.8
1.5
1.1
1.3
1
1
1
1.2
1
1
1
1
1
1
1
1
1
1
1
12
10.7
9.7
11 1
9.2
9.3
9.7
1
1
1
1
1
1
1
1.2
1.4
1
1
1.7
1.7
1
1.9
1.3
1
1
1.2
1
1
1.7
1
3.1
2
22
44
4.2
2.2
4
1
1
1
1
1
1.2
1.2
1
1.1
1
4.1
39
23
1.4
26
13.3
10.9
12
12.1
10.4
92
12.4
1
1
1
1
1
1
1
1
1.1
1.6
day
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
source file
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
MATRIX
SLOOO
BLOOD
BLOOD
BLOOO
SLOOO
SLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
BLOOO
SLOOO
SLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
SLOOD
BLOOO
BLOOD
BLOOD
SLOOD
BLOOO
BLOOO
BLOOD
SLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOOO
BLOOD
BLOOO
BLOOO
BLOOD
SLOOD
BLOOO
BLOOO
BLOOD
SLOOD
BLOOO
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOO
BLOOO
BLOOD
SLOOD
BLOOO
BLOOO
BLOOD
8LOOO
BLOOD
BLOOD
SLOOO
SLOOD
BLOOD
BLOOD
BLOOO
SLOOD
BLOOD
BLOOO
SLOOO
SLOOD
BLOOD
BLOOO
BLOOO
SLOOD
BLOOD
Adjusted Value (ug/dL)1
18
1.5
1.1
1.3
0.5
1
0.5
1.2
0.5
05
0.5
05
05
05
05
05
0.5
0.5
05
12
107
97
11.1
92
93
9.7
0.5
0.5
0.5
05
05
05
05
1.2
1 4
0.5
0.5
1.7
1.7
05
19
1.3
0.5
0.5
1.2
0.5
0.5
1.7
05
3.1
2
22
4.4
42
2.2
4
05
05
0.5
05
05
12
1.2
1
1.1
0.5
4.1
39
23
1 4
26
13.3
109
12
12.1
104
92
124
0.5
0.5
0.5
0.5
05
05
1
0.5
1.1
16
-------
Sum SUty Ptuu II Eip • Ptfnwton
Dig number «ampl«
material admlnlrtered dosage
qualifier lab result (ug/L) day lourci file
MATRIX
Adjusted Value (ug/dLI*
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
8-990321
8-990312
8-990308
8-990337
8-990302
8-990343
8-990339
8-990319
8-990293
8-990300
8-990322
8-990340
8-990341
8-990310
8-990307
8-990332
8-990342
8-990334
8-990292
8-990311
8-990295
8-990328
8-990325
8-990309
8-990297
8-990347
8-990303
8-990323
8-990338
8-990330
8-990324
8-990346
8-990304
8-990316
8-990320
8-990352
8-990399
8-990401
8-990370
8-990351
8-990360
8-990393
8-990377
6-990368
8-990371
8-990384
8-990349
8-990396
8-990369
8-990383
8-990388
8-990363
8-990380
8-990382
8-990356
8-990381
8-990385
8-990362
8-990359
8-990395
8-990386
8-990397
8-990403
8-990389
6-990376
8-990364
8-990373
8-990398
8-990379
8-990367
8-990392
8-990350
8-990404
8-990387
8-990361
8-990353
8-990355
8-990402
8-990375
8-990366
8-990374
8-990354
8-990372
8-990391
8-990348
8-990394
8-990378
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
a
8
8
8
9
9
9
9
9
10
10
10
10
10
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Patmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
75
75
75
75
75
25
25 <
25 <
25 <
25
75
75
75
75
75
225
225
225
225
225
25
25 <
25
25
25 <
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25 <
25 <
25
25
75
75
75
75
75
25 <
25
25 <
25 <
25
75
75
75 <
75
75
225
225
225
225
225
25
25 <
25 <
25
25
75
75 <
75 <
75
75
225
225
225
225
225
2.1
2.2
3.2
22
3.6
1.3
1
1
1
1.1
2.1
26
2
38
23
37
5.1
4.6
26
49
1.6
1
1.3
12
1
1.7
1.4
1.4
1.7
1.8
5.4
49
4.7
32
3.5
14.2
126
11.9
13.5
129
10.8
15.1
1.8
1
1
1.3
1.4
13
1.6
4
23
1.5
1
1.1
1
1
1.5
36
2
1
3.4
1.5
55
38
4.5
3.7
8.1
2.2
1
1
1.4
1.3
39
1
1
14
3.1
36
59
39
3.8
2.2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
T951206
BLOOO
8LOOD
8LOOD
BLOOO
stooo
SLOOD
BLOOO
BLOOD
BLOOO
SLOOD
8LOOD
BLOOD
SLOOO
SLOOD
8LOOO
BLOOD
BLOOD
8LOOD
BLOOO
BLOOD
BLOOO
SLOOO
8LOOD
BLOOO
BLOOO
8LOOD
8LOOD
BLOOD
BLOOO
BLOOD
SLOOO
BLOOD
BLOOO
81OOD
8LOOO
8LOOO
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOD
8LOOD
BLOOD
BLOOO
BLOOD
8LOOD
8LOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOCK)
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
SLOOO
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
6LOOD
2.1
22
32
22
3.6
1.3
0.5
05
05
1.1
2.1
26
2
38
23
3.7
5.1
46
2.6
49
1.6
0.5
1.3
1.2
0.5
17
1.4
14
1.7
1.8
5.4
49
47
32
35
14.2
126
11.9
13.5
129
108
15.1
0.5
05
05
05
05
18
05
05
13
1.4
1.3
1.6
4
23
1.5
05
1.1
0.5
05
1.5
36
2
0.5
3.4
1.5
5.5
38
45
37
81
22
05
0.5
1.4
1.3
3.9
0.5
05
1.4
3.1
36
59
39
38
22
BLOOD
-------
pig number iimple
material admlnlitered dotage
qualifier lab re»utt (ugiLl day
MATRIX
Adjusted Value (ug/dL)'
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
8-990408
8-990457
8-990449
8-990406
8-990435
8-990422
8-990416
8-990461
8-990429
8-990413
8-990444
8-990420
8-990445
8-990455
8-990437
8-990448
8-990412
8-990456
8-990458
8-990432
8-990426
8-990428
8-990460
8-990454
8-990452
8-990431
8-990427
8-990453
8-990451
8-990415
8-990436
8-990447
8-990405
8-990446
8-990439
8-990424
8-990411
8-990440
8-990409
8-990442
8-990418
8-990407
8-990423
8-990419
8-990430
8-990443
8-990450
8-990421
8-990438
8-990441
8-990459
B-990473
8-990510
8-990503
8-990469
8-990507
8-990481
8-990505
8-990482
8-990480
8-990500
8-990504
8-990491
8-990471
8-990499
8-990485
8-990475
8-990494
8-990496
8-990472
8-990462
8-990492
8-990493
8-990516
8-990508
8-990497
8-990478
8-990513
8-990512
8-990466
8-990477
8-990474
8-990486
8-990514
8-990517
8-990463
8-990488
8-990511
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Patmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Patmerton Loc 2
Palmerton Loc 2
100
100
100
100
100
100
0 <
0 <
0 <
0
0 <
25
25
25
25
25
75
75
75
75
75
25
25 <
25 <
25
25
75
75
75
75
75
225
225
225
225
225
25
25 <
25
25
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
25
25
25 <
25
25
75
75
75
75
75
225
225
225
225
225
13.7
15.1
145
152
13.5
15
1
1
1
0.5
1
1.2
1.7
1.4
1.1
1.8
2.2
29
4.1
3
3.5
1.7
1
1
1.4
1.6
3
34
2.2
6.2
3.2
6
68
91
59
8.2
1.5
1
1.4
1.1
1.5
32
3
2.6
28
3.1
5.2
48
58
3.6
4.2
17.4
135
17.5
16.7
15
13.7
166
1
1
1
1
1
1.5
1.1
2.1
2.1
1.9
2.1
43
4.5
49
3
14
1.1
1
1.3
1.7
22
3.5
39
64
33
5.5
4.3
6.2
5.5
5.4
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
T960105
T960105
T960105
T960105
T960105
T960105
I960 105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
I960 105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
BLOOO
SLOOP
etooo
at DOO
ecooo
8LOOD
8L000
BLOOD
BLOOD
8LOOD
SLOOD
flLOOQ
SLOOO
8LOOD
SLOOD
BLOOO
SLOOO
SLOOD
81.OOO
BLOOD
SLOOO
8LOOD
SLOOO
BLOOD
BLOOD
8LOOD
8LOOD
BLOOD
SLOOO
SLOOO
SLOOO
BLOOD
SLOOO
BLOOD
SLOOO
BLOOD
SLOOO
SLOOO
SLOOD
BLOOD
SLOOO
SLOOO
BLOOD
BLOOD
SLOOO
SLOOD
BLOOO
BLOOD
BLOOO
SLOOD
BLOOO
BLOOD
SLOOO
SLOOO
SLOOD
BLOOD
BLOOO
BLOOD
SLOOD
BLOOD
BLOOO
BLOOD
SLOOD
SLOOO
BLOOD
BLOOO
SLOOD
BLOOO
SLOOO
BLOOO
SLOOD
BLOOO
BLOOO
SLOOO
BLOOD
8LOOD
BLOOD
BLOOO
SLOOD
BLOOO
SLOOO
BLOOD
SLOOD
BLOOD
BLOOO
SLOOD
SLOCK)
8LOQO
13.7
15.1
145
152
135
15
0.5
0.5
0.5
05
0.5
1.2
1.7
1.4
1.1
1.8
2.2
29
41
3
3.5
1 7
0.5
0.5
14
16
3
34
22
62
32
6
68
9.1
59
82
1.5
05
14
1.1
1.5
32
3
26
28
3.1
5.2
48
58
36
42
17.4
13.5
17.5
16.7
15
13.7
16.6
0.5
0.5
0.5
0.5
0.5
1.5
1.1
2.1
21
1.9
21
43
4.5
49
3
14
1.1
0.5
13
1.7
22
3.5
39
64
33
55
4.3
62
55
54
-------
Son Study Ptau II E>p 9 P*n«tm
pig number sample
material admlnlitered dotage
qualifier lab rtiult |ufl/i) day
MATRIX
Adlutted Value (ug/dL)'
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
92S
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
8-990509
8-990467
8-990465
8-990502
8-990484
8-990498
8-990464
8-990489
8-990476
8-990495
8-990490
8-990487
8-990501
8-990470
8-990518
8-990524
8-990562
8-990553
8-990557
8-990566
8-990575
8-990520
8-990556
8-990535
8-990572
8-990555
8-990560
8-990546
8-990565
8-990540
8-990538
8-990545
8-990530
8-990569
8-990573
8-990532
8-990554
8-990567
8-990528
8-990529
8-990542
8-990522
8-990539
8-990574
8-990544
8-990543
8-990552
8-990561
8-990521
8-990531
8-990534
8-990547
8-990551
8-990558
8-990533
8-990526
8-990537
8-990568
8-990550
8-990559
8-990549
8-990519
8-990563
8-990525
8-990536
8-990523
8-990548
8-990623
8-990630
8-990624
8-990618
8-990601
8-990584
8-990616
8-990598
8-990606
8-990577
8-990629
8-990605
8-990621
8-990578
8-990604
8-990589
8-990602
8-990591
8-990595
8-990607
8-990587
8
8
8
a
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
Palmerton Loe 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Patmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Patmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <>
0 <
25
25
25
25
25
75
75
75
75
75
25
25
25 <
25
25
75
75
75
75
75
225
225
225
225
225
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
1
1.3
1.8
1.4
1.4
3.1
2.4
2.9
34
2.7
56
5
46
3.7
59
20.4
16.8
17.7
17.1
169
15.5
17.3
1
1
1
1
1
18
2.3
1.7
2.7
2
22
3.8
5.7
3
3.8
12
1
1
1.1
2.2
28
38
39
6.7
3.6
64
4.7
63
48
5.8
1.6
19
1
1
1.2
2.9
18
2
26
42
8.3
42
6
4.5
54
219
16
167
17.2
187
14.9
18
1
1
1
1
1
1.4
36
1.5
2.6
24
27
5.1
68
43
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
BLOOD
SLOOD
8LOOO
SLOOO
9.000
8LOOD
8LOOD
BLOOD
BLOOD
8LOOD
SLOOD
BLOOD
BLOOD
8LOOD
SLOOO
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
SLOOD
8LOOO
BLOOD
BLOOD
SLOOD
9LOOO
BLOOD
BLOOD
SLOOD
SLOOO
BLOOD
BLOOD
SLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
SLOOD
SLOOO
BLOOD
BLOOD
SLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
SLOOO
SLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
SLOOD
1
1.3
1.8
1 4
14
3.1
24
29
34
27
56
5
46
3.7
59
204
168
17.7
17.1
169
155
17.3
05
05
0.5
1
05
1.8
23
1.7
27
2
22
38
57
3
3.8
1.2
1
05
11
22
28
38
39
67
36
64
4.7
63
48
5.8
1.6
19
1
05
12
29
1.8
2
26
4.2
83
42
6
4.5
54
21.9
16
16.7
17.2
187
149
18
0.5
05
0.5
05
05
1.4
36
1.5
26
24
27
5.1
68
43
-------
Sv*w Study Ptn« II Eiq> 9 Plimpton
pig number samplt
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
8-990596
8-990620
8-990611
8-990586
8-990610
8-990585
8-990592
8-990615
8-990619
8-990612
8-990593
8-990579
8-990632
8-990576
8-990628
8-990608
8-990609
8-990614
8-990590
8-990588
8-990622
8-990631
8-990600
8-990594
8-990583
8-990582
8-990617
8-990603
8-990613
8-990581
8-990599
8-990664
8-990688
8-990685
8-990634
8-990689
8-990684
8-990681
8-990677
8-990671
8-990670
8-990651
8-990675
8-990648
8-990639
8-990647
8-990667
8-990674
8-990661
8-990686
8-990649
8-990683
8-990680
8-990655
8-990682
8-990654
8-990637
8-990653
8-990652
8-990640
8-990645
8-990656
8-990643
8-990650
8-990665
8-990635
8-990663
8-990659
8-990668
8-990657
8-990633
8-990658
8-990678
8-990636
8-990666
8-990644
8-990669
8-990676
8-990679
8-990660
8-990662
8-990638
8-990646
group
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
a
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
material administered dotage qualifier lab reeult (ug/L) day
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
rv
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
75
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
4.7
26
1.7
26
1
1.6
25
59
3.8
6
6.5
7.1
43
6.4
6.1
56
1.7
16
1.9
19
23
3.7
24
1.5
33
32
84
49
58
42
64
22
15.7
17
17.5
18.7
15.5
19.5
1
1
1
1
1
18
2.2
28
2.1
3.1
59
7
69
49
54
24
3
2.2
2.1
24
3.2
56
43
6
3.7
7
44
7.9
6.7
6.3
24
22
2.1
2.2
3.2
4.1
3.5
26
3
44
9.1
6.7
5.7
4.7
6.5
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
source file
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
I960 105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
I960 105
T960105
T960105
T960105
I960 105
I960 105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
T960105
MATRIX Adjusted Value (ug'UL)'
SLOOO
8LOOD
SLOOO
BLOOD
81000
BLOOD
SLOOO
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
BLOOO
8LOOD
8LOOD
BLOOD
8LOOO
8LOOD
8LOOD
BLOOD
BIOOO
8LOOD
BLOOD
BLOOD
BLOOO
8LOOD
BLOOD
BLOOD
BLOOO
8LOOD
BLOOD
BLOOD
BLOOO
8LOOD
8LOOD
SLOOO
BLOOO
81000
8LOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLDOO
8LOOD
BLOOD
BLOOD
BLOOO
8LOOD
8LOOD
BLOOD
BLOOO
SLOOO
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
8LOOO
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
etooo
BLOOD
BLOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
47
26
1.7
2.6
05
16
25
59
38
6
6.5
7.1
43
6.4
6.1
56
1 7
16
19
19
23
3.7
24
1.5
3.3
32
84
4.9
58
4.2
64
22
157
17
17.5
18.7
15.5
19.5
05
0.5
0.5
05
0.5
1 8
2.2
28
2.1
31
59
7
69
49
54
24
3
22
2 1
24
32
56
43
6
3.7
7
44
7.9
67
63
24
2.2
21
22
32
41
35
2.6
3
44
9.1
67
5.7
4.7
65
Non-detects evaluated using 1/2 me quantltatnn limit; laboratory results (ug/L) converted to concentration in blood (ug/dL) by dividing by dilution factor of 1 dL/L
-------
TABLE A-4 BLOOD LEAD OUTLIERS
Swlrw Study Ph»M II Exp » Pihwton
Flagged Data Points
I Outliers (none selected)
test target
material dosage
IV 100
IV 100
IV 100
IV 100
IV 100
IV 100
IV 100
Control 0
Control 0
Control 0
Control 0
Control 0
PbAc 25
PbAc 25
PbAc 25
PbAc 25
PbAc 25
PbAc 75
PbAc 75
PbAc 75
PbAc 75
PbAc 75
Palmerton Loc 2 25
Palmerton Loc 2 25
Palmerton Loc 2 25
Palmerton Loc 2 25
Palmerton Loc 2 25
Palmerton Loc 2 75
Palmerton Loc 2 75
Palmerton Loc 2 75
Palmerton Loc 2 75
Palmerton Loc 2 75
Palmerton Loc 2 225
Palmerton Loc 2 225
Palmerton Loc 2 225
Palmerton Loc 2 225
Palmerton Loc 2 225
Palmerton Loc A 25
Palmerton Loc 4 25
Palmerton Loc 4 25
Palmerton Loc 4 25
Palmerton Loc 4 25
Palmerton Loc 4 75
Palmerton Loc 4 75
Palmerton Loc 4 75
Palmerton Loc 4 75
Palmerton Loc 4 75
Palmerton Loc 4 225
Palmerton Loc 4 225
Palmerton Loc 4 225
Palmerton Loc 4 225
Palmerton Loc 4 225
Actual
Dost*
11950
9913
11367
10887
10149
9426
10235
000
000
000
000
000
2215
2378
2452
2664
2718
as 61
6844
7219
6867
7581
2724
2600
2421
2348
2469
6933
7084
8292
7869
7250
20638
24217
23997
24212
20083
2977
2547
2221
2285
2545
7235
8489
6675
7579
74.90
26586
22051
19262
20443
23902
group
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
pig#
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
-4
0.5
0.5
0.5
0.5
05
0.5
0.5
0.5
05
0.5
05
05
0.5
0.5
05
0.5
05
05
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
05
0.5
05
05
05
0.5
05
0.5
05
0.5
05
05
05
05
0.5
05
05
0.5
0.5
0.5
05
05
0
05
0.5
0.5
0.5
05
1.3
05
05
05
0.5
0.5
05
05
0.5
0.5
05
05
0.5
05
05
05
0.5
05
0.5
0.5
0.5
05
0.5
1.2
05
05
05
1.3
1.8
1.5
1.1
1.3
05
1
05
1.2
0.5
05
0.5
05
05
0.5
0.5
0.5
0.5
0.5
0.5
1
12
10.7
9.7
11.1
92
9.3
97
0.5
0.5
0.5
0.5
05
05
0.5
1.2
14
0.5
05
1.7
1.7
0.5
1.9
1.3
0.5
05
1.2
05
0.5
17
05
3.1
2
22
44
42
22
4
05
0.5
0.5
05
05
1.2
1.2
1
1.1
0.5
4.1
3.9
23
14
26
2
133
10.9
12
12.1
10.4
9.2
12.4
05
0.5
0.5
0.5
05
0.5
1
05
1.1
1.6
2.1
22
32
2.2
3.6
1.3
0.5
0.5
0.5
1.1
2.1
26
2
38
23
37
51
46
26
49
16
05
1.3
12
05
1.7
1.4
1.4
1.7
1.8
5.4
49
47
32
35
BLOOD
3
14.2
126
11.9
13.5
12.9
108
15.1
05
0.5
0.5
05
05
1.8
05
05
1.3
1.4
1.3
1.6
4
2.3
1.5
05
1.1
0.5
0.5
1.5
36
2
05
34
1.5
5.5
38
4.5
»,?
»,1
22
05
0.5
1.4
1.3
$&
05
0.5
1.4
3.1
3.6
$,S
39
38
22
LEAD (ug/dL) BY DAY
5
163
137
15.1
145
152
13.5
15
0.5
05
05
05
05
1.2
1.7
1.4
1.1
1.8
22
29
4.1
3
35
1.7
05
05
1.4
1.6
3
34
22
tt
32
6
68
9.1
59
82
1.5
05
1.4
1.1
1.5
32
3
26
28
3.1
52
48
58
36
42
7
17.4
13.5
17.5
16.7
15
13.7
166
0.5
0.5
05
05
05
1.5
1.1
21
21
19
2.1
43
45
49
3
1.4
1.1
05
1.3
1.7
22
35
39
«,*
33
55
43
62
5.5
54
1
1 3
1.8
1.4
14
3.1
24
29
34
27
56
5
46
3.7
59
9
204
168
177
17.1
169
155
17.3
05
0.5
0.5
1
05
1.8
23
17
27
2
22
38
5.7
3
38
12
1
05
1.1
22
28
38
39
s;r
3.6
64
4.7
6.3
48
58
1.6
1.9
1
0.5
1.2
29
18
2
26
42
8.3
4.2
6
45
54
12
21 9
16
167
17.2
18.7
14.9
18
05
05
05
0.5
0.5
1.4
3.6
1.5
26
24
vt
5.1
«,a
43
4.7
26
1.7
26
0.5
1.6
ts
59
38
6
65
7.1
43
64
6.1
56
1.7
1.6
1.9
1.9
23
37
2.4
1.5
33
32
84
49
58
42
64
15
22
157
17
17.5
187
15.5
195
0.5
05
05
05
05
1.8
2.2
28
2.1
3.1
59
7
69
49
54
24
3
22
21
24
3.2
5.6
4.3
6
37
7
44
79
67
6.3
24
22
2.1
22
32
41
35
26
3
44
9.1
67
57
47
65
* Average Time and Weight-Adjusted Dose for Each Pig
-------
Swine Study Phase II Exp 9 Palmerton
TABLE A-5 RATIONALE FOR PbB OUTLIER DECISIONS
No PbB Outliers Selected for this Study
-------
Swine Study Phase II Exp 9 Palmerton
TABLE A-6 Area Under Curve Determinations
Calculated using interpolated values for missing or excluded data
AUC (ug/dL-days) For Time Span Shown
pig*
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
0-1
6.25
5.60
5.10
5.80
4.85
5.30
5.10
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.85
0.95
0.50
0.50
1.10
1.10
0.50
1.20
0.90
0.50
0.50
0.85
0.50
0.50
1.45
0.50
1.80
1.25
1.75
3.10
2.85
1.65
2.65
0.50
0.75
0.50
0.85
0.50
0.85
0.85
0.75
0.80
0.50
2.30
2.20
1.40
0.95
1.55
1-2
12.65
10.80
10.85
11.60
9.80
9.25
11.05
0.50
0.50
0.50
0.50
0.50
0.50
0.75
0.85
1.25
1.05
1.30
1.95
2.45
1.35
2.75
1.30
0.50
0.50
0.85
0.80
1.30
2.15
1.25
3.45
2.15
2.95
4.75
4.40
2.40
4.45
1.05
0.50
0.90
0.85
0.50
1.45
1.30
1.20
1.40
1.15
4.75
4.40
3.50
2.30
3.05
2-3
13.75
11.75
11.95
12.80
11.65
10.00
13.75
0.50
0.50
0.50
0.50
0.50
1.15
0.75
0.50
1.20
1.50
1.70
1.90
3.60
2.25
2.55
0.90
0.80
0.50
0.50
1.30
2.85
2.30
1.25
3.60
1.90
4.60
4.45
4.55
3.15
6.50
1.90
0.50
0.90
1.30
0.90
2.80
0.95
0.95
1.55
2.45
4.50
5.40
4.30
3.50
2.85
3-5
30.50
26.30
27.00
28.00
28.10
24.30
30.10
.00
.00
.00
.00
.00
3.00
2.20
1.90
2.40
3.20
3.50
4.50
8.10
5.30
5.00
2.20
1.60
1.00
1.90
3.10
6.60
5.40
2.70
9.60
4.70
11.50
10.60
13.60
9.60
16.30
3.70
1.00
1.90
2.50
2.80
7.10
3.50
3.10
4.20
6.20
8.80
10.70
9.70
7.40
6.40
5-7
33.70
27.20
32.60
31.20
30.20
27.20
31.60
1.00
1.00
1.00
1.00
1.00
2.70
2.80
3.50
3.20
3.70
4.30
7.20
8.60
7.90
6.50
3.10
1.60
1.00
2.70
3.30
5.20
6.90
6.10
12.60
6.50
11.50
11.10
15.30
11.40
13.60
2.50
1.80
3.20
2.50
2.90
6.30
5.40
5.50
6.20
5.80
10.80
9.80
10.40
7.30
10.10
7-9
37.80
30.30
35.20
33.80
31.90
29.20
33.90
1.00
1.00
1.00
1.50
1.00
3.30
3.40
3.80
4.80
3.90
4.30
8.10
10.20
7.90
6.80
2.60
2.10
1.00
2.40
3.90
5.00
7.30
7.80
13.10
6.90
11.90
9.00
12.50
10.30
11.20
2.60
3.20
2.80
1.90
2.60
6.00
4.20
4.90
6.00
6.90
13.90
9.20
10.60
8.20
11.30
9-12
63.45
49.20
51.60
51.45
53.40
45.60
52.95
1.50
1.50
1.50
2.25
1.50
4.80
8.85
4.80
7.95
6.60
7.35
13.35
18.75
10.95
12.75
5.70
4.05
4.65
2.40
5.70
7.95
14.55
11.55
19.05
15.15
20.25
13.50
19.05
16.35
17.10
4.95
5.25
4.35
3.60
5.25
9.90
6.30
5.25
8.85
11.10
25.05
13.65
17.70
13.05
17.70
12-15
65.85
47.55
50.55
52.05
56.10
45.60
56.25
1.50
1.50
1.50
1.50
1.50
4.80
8.70
6.45
7.05
8.25
12.90
18.15
20.55
13.80
15.15
7.50
7.05
7.20
3.90
6.00
8.55
17.25
12.15
18.00
15.30
21.15
13.05
21.45
19.20
17.85
6.15
5.70
6.00
6.15
8.25
11.70
8.85
6.15
9.45
11.40
26.25
17.40
17.25
13.35
19.35
AUC Total
(ug/dL-days)
263.95
208.70
224.85
226.70
226.00
196.45
234.70
7.50
7.50
7.50
8.75
7.50
20.75
27.95
22.65
28.80
28.70
35.85
56.25
73.35
49.95
52.70
24.20
18.20
16.35
15.50
24.60
37.95
57.30
43.30
81.20
53.85
85.60
69.55
93.70
74.05
89.65
23.35
18.70
20.55
19.65
23.70
46.10
31.35
27.80
38.45
45.50
96.35
72.75
74.85
56.05
72.30
-------
TABLE A - 7 TISSUE LEAD DATA
S**» Study Pt«u II En> 9 PdmMm
pig number sample
material admlnlatered dotage
qualifier lab rttult (uq/Ll d«y
tource flit
MATRIX
Adjusted Value'
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
323
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
8-990853
8-990878
8-990872
8-990870
8-990886
8-990856
8-990857
8-990852
8-990888
8-990863
8-990889
8-990891
8-990879
8-990896
8-990887
8-990871
8-99085*
8-990854
8-990877
8-990859
8-990851
8-990845
8-990862
B-990865
8-990882
8-990864
8-990880
8-990894
8-990867
8-990869
8-990890
8-990899
8-990883
8-990868
8-990885
8-990876
8-990895
8-990849
8-990866
8-990892
8-990848
8-990874
8-990846
8-990855
8-990881
8-990898
8-990893
8-990884
8-990847
8-990861
8-990873
8-990860
8-990823
8-990815
8-990795
8-990798
8-990811
8-990792
8-990819
8-990804
8-990800
8-990791
8-990806
8-990801
8-990790
8-990817
8-990830
8-990826
8-990842
8-990843
8-990802
8-990832
8-990840
8-990824
8-990836
8-990805
8-990799
8-990835
8-990814
8-990825
8-990828
8-990829
8-990803
8-990834
8-990837
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
1
1
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
IV
IV
IV
IV
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
IV
rv
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
25
25 <
25
25
25
75
75
75
75
75
225
225
225
225
225
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
25
25
25
25
25
75
75
75
75
75
225
112
848
105
92
832
843
82
2
2
2
2
2
3.5
3.3
72
62
7.3
96
9.2
14.5
14.2
84
3.1
2
49
27
56
5.7
96
5.9
84
52
12.3
15.5
18.5
17.3
10.5
34
4.5
3.5
29
3.9
6.3
7.5
6.3
5.2
5
123
163
14.1
99
115
184
170
120
125
112
111
113
2.3
2
2
2
2
3
57
6
55
11.7
18.7
185
31
153
246
29
4.1
24.1
64
109
102
476
81
47.6
136
26.1
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960131F
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
'FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KtONEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KtONEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
56
424
52.5
46
41 6
4215
41
0.5
05
0.5
0.5
0.5
1 75
165
36
3.1
365
48
46
725
7.1
42
1 55
0.5
245
1 35
28
285
48
295
42
2.6
6.15
775
925
865
525
1.7
225
1.75
1.45
1 95
315
3.75
3.15
26
2.5
615
8.15
705
495
5.75
1840
1700
1200
1250
1120
1110
1130
23
10
10
10
10
30
57
60
55
117
187
185
310
153
246
29
41
241
64
109
102
476
81
476
136
261
-------
Stint Study Ptuu II Eip 9 PdnwUn
pig number aample group material administered dotage
qualifier lab result fug/Li day source file
MATRIX
Adjusted Value*
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
907
912
919
930
942
943
953
901
902
920
925
928
905
909
927
931
940
923
933
948
950
956
911
929
934
947
954
903
910
938
951
955
906
908
916
918
922
913
914
932
937
946
924
926
944
949
957
917
921
939
941
945
8-990831
8-990794
8-990793
8-990808
8-990813
8-990818
8-990812
8-990807
8-990816
8-990820
8-990839
8-990796
8-990809
8-990821
8-990827
8-990833
8-990838
8-990822
8-990797
8-990765
8-990737
8-990742
8-990752
8-990746
8-990751
8-990789
8-990743
8-990735
8-990736
8-990766
8-990753
8-990769
8-990772
8-990762
8-990763
8-990778
8-990784
8-990775
8-990740
8-990781
8-990768
8-990756
8-990744
8-990755
8-990749
8-990738
8-990774
8-990741
8-990786
8-990747
8-990761
8-990767
8-990760
8-990757
8-990764
8-990782
8-990759
8-990785
8-990754
8-990750
8-990773
8-990758
8-990770
8-990788
8-990787
8-990777
8-990771
8-990783
8-990779
8-990745
8-990739
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
10
10
10
10
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
IV
IV
rv
rv
IV
IV
IV
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
Palmerton Loc 4
225
225
225
225
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
100
100
100
100
100
100
100
0 <
0 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
18.3
25.5
21.9
19.1
3.3
5.4
4.8
3.9
144
9.9
8.2
11.5
7.7
57
228
24.4
28.2
13
161
166
155
241
160
88
149
103
2
2
2
2
2
4.1
5.7
6.1
39
11.1
20
21.2
32.6
10.2
18.4
4.4
3.9
12.8
9
5.5
12.3
445
5.8
392
92
23.9
222
35.1
22
197
61
48
3.2
35
81
7.1
13.1
11.5
167
6.2
268
288
27.7
123
253
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
KIDNEY
KIDNEY
KIDNEY
KIONEY
KIDNEY
KfOMEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIONEY
KIONEY
KIDNEY
KIONEY
KIONEY
KIONEY
KE3NEY
KIONEY
LWER
LIVER
LWER
IWER
LWER
LIVER
tWER
LIVER
LIVER
LIVER
LIVER
LWER
LWER
LWER
LIVER
LIVER
LWER
LIVER
LIVER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LIVER
LWER
tWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
LWER
183
255
219
191
33
54
48
39
144
99
82
115
77
57
228
244
282
130
161
1660
1550
2410
1600
880
1490
1030
10
10
10
10
10
41
57
61
39
111
200
212
326
102
184
44
39
128
90
55
123
445
58
392
92
239
222
351
220
197
61
48
32
35
81
71
131
115
167
62
268
288
277
123
253
Non-detects evaluated using 1/2 the quantitatton limtt Laboratory results (ug/L) converted to tissue concentrations by dividing by sample dilution factors of
0 1 kg/L (Irver, kidney) or 2 g/L (ashed bone). Final units are ug Pb/kg wet weight (liver, kidney) or ug Pb/g ashed bone (femur)
-------
Swte Study PhiM II Exp t famtAat
TABLE A-8 SUMMARY OF ENDPOINT OUTLIERS
J Selected Outliers
test target Actual
material dosage Dose* group pig#
IV 100 119.50 907
IV 100 99.13 912
IV 100 113.67 919
IV 100 10887 930
IV 100 101.49 942
IV 100 9426 1 943
IV 100 10235 1 953
Control 0 0.00 2 901
Control 0 0.00 2 902
Control 0 0.00 2 920
Control 0 000 2 925
Control 0 000 2 928
PbAc 25 2215 3 905
PbAc 25 2376 3 909
PbAc 25 2452 3 927
PbAc 25 2664 3 931
PbAc 25 2718 3 940
PbAc 75 8861 4 923
PbAc 75 6844 4 933
PbAc 75 72.19 4 948
PbAc 75 6867 4 950
PbAc 75 75.81 4 956
Palmerton Loc 2 25 27.24 5 91 1
Palmerton Loc 2 25 2600 5 929
Palmerton Loc 2 25 24.21 5 934
Palmerton Loc 2 25 23.48 5 947
Palmerton Loc 2 25 24 69 5 954
Palmerton Loc 2 75 69 33 6 903
Palmerton Loc 2 75 70.84 6 910
Palmerton Loc 2 75 82 92 6 938
Palmerton Loc 2 75 78.69 6 951
Palmerton Loc 2 75 72.50 6 955
Palmerton Loc 2 225 206.38 7 906
Palmerton Loc 2 225 242.17 7 908
Palmerton Loc 2 225 239.97 7 916
Palmerton Loc 2 225 242.12 7 918
Palmerton Loc 2 225 200.83 7 922
Palmerton Loc 4 25 29.77 8 913
Palmerton Loc 4 25 2547 8 914
Palmerton Loc 4 25 22.21 8 932
Palmerton Loc 4 25 22.85 8 937
Palmerton Loc 4 25 25 45 8 946
Palmerton Loc 4 75 7235 9 924
Palmerton Loc 4 75 84 89 9 926
Palmerton Loc 4 75 6675 9 944
Palmerton Loc 4 75 7579 9 949
Palmerton Loc 4 75 74 90 9 957
Palmerton Loc 4 225 265.86 10 917
Palmerton Loc 4 225 22051 10 921
Palmerton Loc 4 225 19262 10 939
Palmerton Loc 4 225 20443 10 941
Palmerton Loc 4 225 239 02 1 0 945
MEASUREMENT ENDPOINT
Blood
26395
2087
22485
226.7
226
196.45
2347
7.5
75
7.5
875
7.5
2075
2795
22.65
288
287
35 85 |c
5625
73 35 |b
4995
527
24.2
182
16.35
15.5
246
3795
573
43.3
81.2 |b
5385
856
6955
937
7405
8965
23.35
18.7
2055
1965
237
46.1
31.35
278
3845
455
9635
7275
7485
5605
723
Femur
56
42.4
525
46
416
42.15
41
05
0.5
0.5
05
0.5
1.75
1 65
36
3.1
365
4.8
46
725
7.1
42
1.55
05
245
1 35
28
2.85
48
295
4.2
26
615
7.75
925
865
5.25
1.7
225
1 75
1 45
1 95
3.15
375
315
2.6
25
615
8.15
705
495
575
Liver
1660
1550
2410
1600
880
1490
1030
10
10
10
10
10
41
57
61
39
111
200
212
326 |b
102
184
44
39
128
90
55
123
445 |b
58
392 |b
92
239
222
351
220
197
61
48
32
35
81
71
131
115
167
62
268
288
277
123 |b
253
Kidney
1840
1700
1200
1250
1120
1110
1130
23
10
10
10
10
30
57
60
55
117
187
185
310 |b
153
246
29
41
241
64
109
102
476 |b
81
476 |b
136
261
183
255
219
191
33
54
48
39
144 |b
99
82
115
77
57
228
244
282 |b
130
161
a a priori outlier determinations (none selected in this study)
b Outside 95% Prediction Intervals
c In this dose group, 3 of 5 values are close to the mean. Of the remaining two one is above and one is below the mean. The one high value
is outside the 95% Prediction Interval, but the low value is inside the 95% Prediction Interval Thus, the default rule is
to exclude the high point and retain the low data point However, retaining the low point in the absence of the high point causes
the best fit curve to plateau at a much lower level (58 ug/dL-days) than seen for PbAc in other studies (e.g , 1 59 ug/dL-days)
In fact, the best fit line for PbAc drops below the best fit line for test material, yielding RBA values that are greater than one.
This is considered to be biologically implausible and inappropriate Therefore, the low data point and the high data point
were both excluded. This yielded a best fit more nearly in accord with other studies (plateau = 118 ug/dL-days), and yielded
RBA values considered to be more plausible
-------
TABLE A-9 Best Curve Fit Parameters
BLOOD
PbAc Curve -
a
b
c
d
R2
Loc 2 Curve -
a
b
c
d
R2
Loc 4 Curve -
a
b
c
d
R2
Exp
7.22
104
0.0081
0.982
Exp
7.22
104
0.006
0.935
Exp
7.22
104
0.0047
0.934
Equations Used
EXP Y=a+c*
BONE
PbAc Curve - Linear
a 0.87
b 0.0634
c
d
R2 0.771
Loc 2 Curve - Linear
a 0.87
b 0.0298
c
d
R2 0.904
Loc 4 Curve - Linear
a 0.87
b 0.0249
c
d
R2 0.879
(1-exp(-d*dose))
LIN Y=a+b*dose
LIVER
PbAc Curve - Linear
a
b
c
d
R2
18.41
2.036
0.854
Loc 2 Curve - Linear
a
b
c
d
R2
18.41
1.014
0.843
Loc 4 Curve - Linear
a
b
c
d
R2
18.41
1.103
0.913
KIDNEY
PbAc Curve •
Linear
a
b
c
d
R2
25.06
2.14
0.87
Loc 2 Curve - Linear
a
b
c
d
R2
25.06
0.896
0.618
Loc 4 Curve - Linear
a
b
c
d
R2
25.06
0.725
0.87
-------
TABLE A-10 Relative Bioavailability of Lead in Test Materials
Endpoint
Blood
Kidney
Liver
Bone
Test Material
Location 2
0.74
0.42
0.50
0.47
Location 4
0.58
0.34
0.54
0.39
Definitions
Plausible Range:
Preferred Range:
Suggested Point Est:
RBA(Blood) to mean RBA for Tissues
RBA(Blood) to (RBA(Blood) + RBA(Tissues))/2
1/2(RBA(Blood) + (RBA(Blood)+RBA(Tissues))/2)
Relative Bioavailability
Plausible Range
Preferred Range
Point Estimate
Location 2
0.74 0.46
0.74 0.60
0.67
Location 4
0.58 0.42
0.58 0.50
0.54
Absolute Bioavailability
Plausible Range
Preferred Range
Point Estimate
Location 2
37% 23%
37% 30%
34%
Location 4
29% 21%
29% 25%
27%
-------
Swine Study Phase II Exp 9 Palmerton
TABLE A-11 INTRALABORATORY DUPLICATES
RPD = Relative Percent Difference
RPD = 100*[Orig-Dup]/((Orig+Dup)/2
* Non detects evaluated at 1/2 DL
Orig. pig number
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
930
916
917
jroup
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
1
7
10
material administered
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
IV
Palmerton
Palmerton
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
Loc2
Loc4
dosage
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
100
25
0
day
-4
-4
-4
0
0
0
1
1
1
2
2
2
3
3
3
5
5
5
7
7
7
9
9
9
12
12
12
15
15
15
15
15
15
15
15
15
15
15
15
matrix
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
FEMUR
FEMUR
FEMUR
KIDNEY
KIDNEY
KIDNEY
LIVER
LIVER
LIVER
Duplicate Value*
0.5
0.5
0.5
0.5
1.7
0.5
11.5
3.6
3.4
14.4
4.7
5.6
15.2
5
6.3
16.1
10.2
6.3
16.4
6.9
6.1
17.3
6.5
7.5
19
7.1
8.4
17.9
8.2
9.3
83
19.1
12.9
134
26
27.1
115
33
25.6
Original Value*
0.5
0.5
0.5
0.5
1.5
0.5
11.1
4.2
4.1
12.1
4.6
5.4
13.5
4.5
3.6
14.5
9.1
5.2
16.7
6.2
5.6
17.1
63
8.3
17.2
6.4
8.4
17.5
7.9
9.1
92
18.5
12.3
125
25.5
22.8
160
35.1
26.8
Average
0.5
0.5
0.5
0.5
1.6
0.5
11.3
3.9
3.75
13.25
4.65
5.5
14.35
4.75
4.95
15.3
9.65
5.75
16.55
6.55
5.85
17.2
6.4
7.9
18.1
6.75
8.4
17.7
8.05
9.2
87.5
18.8
12.6
129.5
25.75
24.95
137.5
34.05
26.2
RPD
0%
0%
0%
0%
-13%
0%
-4%
15%
19%
-17%
-2%
-4%
-12%
-11%
-55%
-10%
-11%
-19%
2%
-11%
-9%
-1%
-3%
10%
-10%
-10%
0%
-2%
-4%
-2%
10%
-3%
-5%
-7%
-2%
-17%
33%
6%
5%
Avg RPD
-0.054 BLOOD
0.008 FEMUR
-0087 KIDNEY
0.145 LIVER
-------
TABLE A-12 CDC STANDARDS
Sample ID
9.1
9.1
9.1
9.1
9.1
9.2
9.2
9.2
9.2
9.2
9.2
9.2
9.2
9.3
9.3
9.3
9.3
9.3
9.3
9.3
Day Q
-4 <
0
1
3 <
9 <
-4
0
1
2
5
7
12
15
2
3
5
7
9
12
15
Averages
Measured
Low Std Med Std
1.0
1.3
1.0
1.0
1.0
3.2
3.8
4.3
4.0
4.3
4.6
4.5
4.1
1.1 4.1
Hlqh Std
12.7
13.4
16.1
15.3
12.9
16.5
14.9
Nominal
Concentration
1.7
1.7
1.7
1.7
1.7
4.8
4.8
4.8
4.8
4.8
4.8
4.8
4.8
14.9
14.9
14.9
14.9
14.9
14.9
14.9
14.5 NA
-------
TABLE A-13 INTERLABORATORY COMPARISON
Tag
Number
8-990127
8-990154
8-990196
8-990225
8-990269
8-990280
8-990311
8-990332
8-990364
8-990371
8-990409
8-990417
8-990475
8-990496
8-990539
8-990555
8-990585
8-990591
8-990647
8-990659
Pig
Number
916
910
927
903
903
917
922
906
951
920
932
9.2
931
923
903
925
954
923
927
922
Group
7
6
3
6
6
10
7
7
6
2
8
3
4
6
2
5
4
3
7
Material
Administered
Palmerton Loc 2
Palmerton Loc 2
PbAc
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 4
Palmerton Loc 2
Palmerton Loc 2
Palmerton Loc 2
Control
Palmerton Loc 4
PbAc
PbAc
Palmerton Loc 2
Control
Palmerton Loc 2
PbAc
PbAc
Palmerton Loc 2
Dosage
225
75
25
75
75
225
225
225
75
0
25
25
75
75
0
25
75
25
225
Qualifier
CDC
U
U
U
U
U
U
EPA
<
<
<
<
<
<
<
CDC
0.6
0.6
0.6
0.6
1.1
4.0
5.5
4.1
5.5
0.6
1.3
4.8
2.2
2.1
2.8
0.6
2.3
3.2
2.4
5.6
Result
EPA
1.0
1.0
1.0
1.0
1.0
4.1
4.9
3.7
3.4
1.0
1.4
4.3
2.1
2.1
2.8
1.0
1.6
2.7
2.8
6.3
Average
0.8
0.8
0.8
0.8
1.1
4.1
5.2
3.9
4.5
0.8
1.4
4.6
2.2
2.1
2.8
0.8
2.0
3.0
2.6
6.0
RPD
50
50
50
50
-10
2
-12
-10
-47
50
7
-11
-5
0
0
50
-36
-17
15
12
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-1 PbAc and IV Groups by Day
Raw Data
CO
JO
Q.
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-2 Palmerton Location 2 Groups by Day
Raw Data
20
15
10
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-3 Palmerton Location 4 Groups By Day
Raw Data
20
m
£
15
10
—B 913
—A 914
—X 932
—X 937
—* 946
- *- - -924
- - A- - -926
- - X- - -944
949
- » - -957
-• 917
-H- 921
939
941
—• 945
-------
Swine Study Phase II Exp 9 Palmerton
-2
-ae-
18
16
14
12
10
FIGURE A-4 Group Mean PbB vs. Day
Raw Data
10
12
14
16
- * - iiv
B 2 Control
~ A ~ 3 RbAc (25)
- X - 4PbAc(75)
X 5 Palmerton 2 (25)
• 6 Palmerton 2 (75)
1 7 Palmerton 2 (225)
— 8 Palmerton 4 (25)
—-— 9 Palmerton 4 (75)
—O— 10 Palmerton 4 (225)
Study Day
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-5 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
OJ
•
O)
O
CO
TJ
O
O
100
80-
60-
40-
5 20H
MATERIAL: PbAc
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
20
40 60
Dose (ug Pb/kg-day)
80
100
Parameters
a
c
d
Value
7.22
104
0.0081
Std. Error
fixed value
fixed value
0.0003
95% Confidence Limits
—
-
0.0075
—
-
0.0087
Adj R
0.982
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-6 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Palmerton Location 2
ENDPOINT: Blood Lead ADC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
CD
0)
O
<
•o
CO
o>
00
100 150
Dose (ug Pb/kg-day)
200
250
Parameters! Value
a
c
d
7.22
104
0.006
Std. Error
fixed value
fixed value
0.0004
95% Confidence Limits
—
—
0.0051
—
-
0.0069
AdJ R
0.935
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-7 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Palmerton Location 4
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
re
•o
05
O
03
T3
O
£
CO
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
c
d
Value
7.22
104
0.0047
Std. Error
fixed value
fixed value
0.0003
95% Confidence Limits
—
—
0.0041
_
—
0.0053
Adj R2
0.934
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-8 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
V)
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-9 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
T3
O>
to
o>
T3
to
CD
0)
c
o
CD
10
9-
8-
7-
6-
5-
4-
3-
2-
1-
0
MATERIAL: Palmerton Location 2
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
50
100 150
Dose (ug Pb/kg-day)
200
250
Parameters
a
b
Value
0.87
0.0298
Std. Error
fixed value
0.0016
95% Confidence Limits
—
0.0264
—
0.0331
I Adj R2 0.903 |
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
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Swine Study Phase II Exp 9 Palmerton
FIGURE A-10 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
co 6-
O)
T3
CO
CD
CD
c
o
CO
4-
3-
2-
1-
MATERIAL: Palmerton Location 4
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters | Value | Std. Error
a
b
0.87
0.025
fixed value
0.0015
95% Confidence Limits
—
0.022
—
0.028
Adj R
0.879
Generated using Table Curve 20 v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-11 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
I
o>
0)
0)
250
200-
150-
100-
50-
20
40 60
Dose (ug Pb/kg-day)
80
Parameters
a
b
Value
18.41
2.036
Std. Error
fixed value
0.17
95% Confidence Limits
—
1.67
—
2.4
| Adj R2 0.854 |
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
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Swine Study Phase II Exp 9 Palmerton
FIGURE A-12 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
250-
13 200-
a;
l! 150-
0)
J 100
50-^
0
0
MATERIAL: Palmerton Location 2
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
50
100 150
Dose (ug Pb/kg-day)
200
250
Parameters
a
b
Value
18.41
1.014
Std. Error
fixed value
0.074
95% Confidence Limits
—
0.858
—
1.169
AdjR2
0.843
Generated using Table Curve 20 v. 3.0. Outliers represented by"+".
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Swine Study Phase I! Exp 9 Palmerton
FIGURE A-13 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
ra
05
•o
CO
CD
350
300-
250-
200-
150-
100-
50-
0
MATERIAL: Palmerton Location 4
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
18.41
1.103
Std. Error
fixed value
0.058
95% Confidence Limits
—
0.982
—
1.225
AdjFT
0.9131
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
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Swine Study Phase II Exp 9 Palmerton
FIGURE A-14 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
I
O)
O)
•a
co
0)
OJ
;g
350
300-
250-
200-
150-
100-
50-
20
40 60
Dose (ug Pb/kg-day)
80
Parameters | Value
a
b
25.06
2.14
Std. Error
fixed value
0.172
95% Confidence Limits
—
1.768
—
2.511
Adj R
0.87
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-15 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
300
y 250-
o> 200 H
a.
g* 150H
CD
-------
Swine Study Phase II Exp 9 Palmerton
FIGURE A-16 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Palmerton Location 4
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
o>
Q.
O)
T3
CO
0>
300
250-
200-
150-
100-
50-
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
25.06
0.725
Std. Error
fixed value
0.051
95% Confidence Limits
—
0.618
—
0.832
AdjR2
0.87
Generated using Table Curve 2D v. 3.0. Outliers represented by "+"
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