BIOAVAILABILITY OF LEAD IN SOIL AND MINE WASTE
FROM THE CALIFORNIA GULCH NPL SITE
LEADVILLE, CO
June 1998
II BIOAVAILABILITY INVESTIGATIONS
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BIO AVAILABILITY OF LEAD IN SOIL AND MINE WASTE
FROM THE CALIFORNIA GULCH NPL SITE
LEADVILLE, COLORADO
June 1998
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
ISSI Consulting Group, Inc.
Denver, Colorado
Document Control Number 04800-030-0178
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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.
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. Stockham, DVM, MS, DACVP, University of Missouri, Columbia,
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 four different test materials collected at the California Gulch
Superfund Site, located in and about the community of Leadville, Colorado. 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 four test materials were each from different areas of the site. The following table
summarizes the nature of these samples:
Sample Name
Phase I Residential
Composite
Fe-Mn-Pb Oxide
AV Slag
Oregon Gulch
Sample Description
Composite of surface soil from 28 different locations
in the main residential area of Leadville
Composite of three surface soils from near the Lake
Fork Trailer Park
Sample of fines located at the base of a large pile of
water-quenched slag at the former AV Smelter
Composite of several subsamples of tailings material
collected from the Oregon Gulch tailings
impoundment
Lead Concentration
7,510ppm
4,320 ppm
10,600 ppm
1,270 ppm
The gastrointestinal absorption of lead in these test materials was investigated in a series of
three different studies. The designs of these studies were generally similar, with groups of
4-5 swine being exposed to test material and reference material (lead acetate) for 15 days.
However, there was some variation in the dose levels administered, as summarized below:
Study
7
8
12
Test Materials
Administered
Phase I Composite
Fe-Mn-Pb Oxide
AV Slag
Oregon Gulch
Dose Level (ug Pb/kg-day)
Test Material
0, 25, 75, 225
0, 25, 75, 225
0, 225
Lead Acetate
0, 25, 75
0, 25, 75
0, 25, 75, 225
The amount of lead absorbed by each animal in each study 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 materials 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 a test material was absorbed equally as well as lead from lead acetate, and 50%
ES-1
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behaved as if it were not available for absorption. Thus, if lead acetate were 40% absorbed
into the body, about 20% of the lead in the test material would be absorbed into the body.
The KB A results for the four samples from the California Gulch site are summarized below:
Measurement
Endpoint
Blood Lead AUC
Liver Lead
Kidney Lead
Bone Lead
Test Material
Phase I
Composite
0.71
0.92
0.91
0.62
Fe-Mn-Pb
Oxide
0.87
0.96
1.24
0.84
AV
Slag
0.20
0.11
0.10
0.18
Oregon
Gulch
0.06
0.05
0.04
0.004
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
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
Phase I
Composite
0.71 -0.82
0.71 -0.76
0.74
Fe-Mn-Pb
Oxide
0.87- 1.0
0.87 - 0.94
0.90
AV
Slag
0.13 -0.20
0.16-0.20
0.18
Oregon
Gulch
0.03 - 0.06
0.05 - 0.06
0.06
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:
ABA5ni, = ABA
soluble
RBA
soil
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 test soils are as follows:
ES-2
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Absolute
Unavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Phase I
Composite
36% -41%
36%-38%
37%
Fe-Mn-Pb
Oxide
43% -51%
43% -47%
45%
AV
Slag
6%-10%
8%-10%
9%
Oregon
Gulch
2% -3%
2% -3%
3%
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-3
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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 1ฐ
2.4 Dosing 10
2.5 Collection of Biological Samples 15
2.6 Preparation of Biological Samples for Analysis 15
2.7 Lead Analysis 16
3.0 DATA ANALYSIS - 17
3.1 Overview 17
3.2 Fitting the Curves 17
3.3 Responses Below Quantitation Limits 18
3.4 Quality Assurance 18
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 28
5.0 REFERENCES 30
APPENDIX TITLE
1 Detailed Data Summary
Section A: Study 7
Section B: Study 8
Section C: Study 12
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LIST OF TABLES
TABLE
TITLE
PAGE
2-1 Metal Analysis of Test Materials 5
2-2 Typical Feed Composition 11
2-3 Dosing Protocol - Study 7 12
2-4 Dosing Protocol - Study 8 13
2-5 Dosing Protocol - Study 12 14
3-1 Summary of QA Results 19
LIST OF FIGURES
FIGURE TITLE PAGE
2-1 Lead Minerals Observed in Site Soils 6
2-2 Lead Particle Size Distribution 7
2-3 Body Weights of Test Animals 9
4-1 Group Mean Blood Lead by Day 22
4-2 Blood Lead Dose-Response 23
4-3 Bone Lead Dose-Response 24
4-4 Liver Lead Dose-Response 25
4-5 Kidney Lead Dose-Response 26
11
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BIOAVAILABILITY OF LEAD IN SOIL AND MINE WASTE
FROM THE CALIFORNIA GULCH NPL SITE
LEADVILLE, COLORADO
1.0 INTRODUCTION
Absolute and Relative Bioavailability
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 preferred when referring to the amount of lead that dissolves under a
specified set of test conditions.
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).
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Using Bioavailabilitv 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 ABA of a test
soil is as follows:
l ABAsoluble RBAsoii
where:
ABAsoil = Absolute bioavailability of lead in soil ingested by a child
ABAsolubie = Absolute bioavailability in children of some dissolved or fully
soluble form of lead
RBAsoil = RBA for soil measured in swine
Based on available information in the literature on lead absorption in humans, 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:
ABAsoil = 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%/50% = 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 hazards 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 hazards 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). This 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
2.1.1 Sample Descriptions
Four different test materials from the California Gulch Superfund Site were collected and
analyzed in this investigation. A description of each of these samples is provided below.
Phase I Residential Soil Composite
This soil sample was collected early in the program, and was used in previous studies referred
to as "Phase I". It consisted of a composite of surface soils (0-6 inches) from 28 different
residential properties within Leadville. Each sub-sample was selected to have a lead
concentration of at least 6,000 ppm, with actual values ranging from 6,380 ppm to 21,380 ppm.
The final lead concentration in the composite sample was 7,510 ppm.
Fe-Mn-Pb Oxide Soil Sample
This sample was a composite of three different surface soil samples (0-6 inches) collected near
the Lake Fork Trailer Park, located southwest of Leadville near the Arkansas River. Because
lead speciation studies indicated that lead in this area consisted largely of iron-lead oxide and
manganese-lead oxide, this sample was referred to as the "Fe-Mn-Pb Oxide" sample. The final
lead concentration in the composite was 4,320 ppm.
AV Smelter Slag Sample
This sample was collected from the toe of a steep slope on the northern edge of a large pile of
water-quenched slag which remains on the property of the former Arkansas Valley (AV)
Smelter, located just west of Leadville. The lead concentration in the sample was 10,600 ppm.
Oregon Gulch Tailings Sample
This sample was a composite of several subsamples of tailings collected from the Oregon Gulch
tailings impoundment located in Oregon Gulch, just south of Leadville. The lead concentration
in the composite sample was 1,270 ppm.
2.1.2 CLP Analyses
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Each of the four different samples were sieved using a 60-mesh nylon screen, 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 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 sieved samples, measured using standard EPA Contract
Laboratory Program (CLP) methods.
2.1.3 Lead Phases
Each test material was analyzed by electron microprobe in order to characterize the lead
minerals present in the sample. The results are summarized in Figure 2-1. The solid bars
represent the length-weighted particle frequency of lead-bearing grains, and the open bars
represent the approximate fraction of the total lead mass accounted for by each phase.
Inspection of these graphs reveals the following main points:
The Phase I Residential Soil Composite contains a variety of different lead
phases, with lead phosphate and iron-lead oxide being most common in terms of
particle frequency. However, the majority of the lead mass is accounted for by
lead phosphate, manganese lead oxide and cerussite (lead carbonate).
The FeMnPb Oxide soil sample is relative more enriched in manganese lead oxide
and iron lead oxide, with manganese lead oxide accounting for most of the
relative lead mass.
As expected, the most common lead-bearing particle type in the AV slag sample
is slag, but because the slag particles contain relatively low concentrations of
lead, the majority of the relative lead mass is present in other forms, mainly iron-
lead oxide and lead arsenic oxide.
Lead in the sample of tailings from the Oregon Gulch impoundment consists
entirely of galena (lead sulfide), both in terms of particle count and relative lead
mass.
2.1.4 Particle Size Distributions
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 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).
Figure 2-2 summarizes the size distribution of lead-bearing particles present in each sample.
As seen, there is a fairly wide size distribution in the Phase I Residential Soil Composite (Panel
A), the FeMnPb Oxide sample (Panel B), and the AV Slag sample (Panel C), although in all
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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)
Residential
Composite
8670
1.8
203
605
0.06
59.9
20100
9.1
2.0
657
68120
7510
9521
7090
1.26
5.6
1500
1.9
43
6560
<0.5
33.7
13738
Fe-Mn-Pb
Oxide
11900
6.0
110
266
1.0
38.5
3930
7.5
6.9
165
27500
4320
2520
1190
4.9
7.5
1770
0.8
16.7
279
3.7
17.9
2650
AV
Slag
20800
57.2
1050
2430
1.2
12.8
117000
43.1
53.8
2080
207000
10600
6360
6910
0.11
7.1
7390
61.3
21.2
4080
1.8
37.2
67300
Oregon
Gulch
248
74.4
1290
14.2
2.0
4.0
8290
8.0
10.1
350
391000
1270
118
126
0.24
28.2
451
0.53
41.7
34.1
0.86
47.7
441
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FIGURE 2-1 LEAD MINERALS OBSERVED IN SITE SOILS
Pane! A: Phase 1 Residential Soil Composite
Lปd Validate
PbSiCM
Ctty
Stag
PbO-Cemulte
Fซ-PtS*ale
Pb Phosphate
Pb Organic
P6ASO
MvPb Oxide
Galena
Fe-PbOjfde
Cemjslte
Pbaarite
Angtosite
Al-Pb Silicate
3
a
a
=
3
^
Lp^m
^
a ,
3
SFreq
DMass
0% 20% 40% 60% 80% 100%
Lead Validate
PHS04
Sag
PbO-Cemwile
Fe-PtSJhte
Pb Phosphate
Mi-PbOnde
Galena
Fe-Pb Odde
Cerrusfte
FtBarlte
Afigtesite
Al-Pb SMcate
0'
Panel C: AV Slag
b
i
3
j HFreq
| DMass
Sfc 20% 40% 60% 80% 100%
LeadVartdale
PbSO4
Claj
Slag
PbO-CemBlte
Fe^PbSuttate
Pfa Phosphate
Pb Organic
PbflSO
Mn-PbCbdde
Galena
Fe-PbCMde
Cemjstte
PaBartts
Angle-ate
Al-Pb Silcal*
0
Panel B: FeMnPb Oxide
mm8&za
\
a
EFreq
DMass
% 20% 40% 60% 80% 100%
Panel D; Oregon Gulch Tailings
Lead Validate
P6S104
PbO-CemsUe
Fe-Pb SJfate
PbPnasphate
Pb Organic
PtASO
Galena
Fe-Pb DM*
PbSarite
Angleslte
Al-PbSiicate
HFreq
D Mass
0% 20% 40% 60% 80% 100%
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FIGURE 2-2 LEAD PARTICLE SIZE DISTRIBUTION
Panel A: Phase 1 Residential Soil Composite
100%
90%
80%
70% \
ซ 60%
= 50%
ฃ 40%
u.
30% +
60%
50%
ง 30%
20-49 50-9S 100-146 150-169 200-249
Particle Size (um)
Panel C: AVSiag
50-89 10O-149 150-199 200-249
Particle Size (um)
60%
50%
40%
30%
20%
10%
Panel B: FeMnPb Oxide
69 10-19 20-49 5O-S9 100-149 150-199 200-249 >250
Particle Size (urn)
Panel D: Oregon Gulch Tailings
20-49 50-99 100-149 150-199 200-249 >250
Particle Size (um)
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cases the majority of all lead-bearing particles are less than 50 um in length. The lead-bearing
galena particles present in the Oregon Gulch tailings sample are especially small, with about
85% being less than 5 um in longest dimension.
2.1.5 Matrix Associations
If lead-bearing grains are entirely encased ("included") in a glassy or rocky matrix, the lead
grains are less likely to be bioavailable that if they are partly or entirely exposed ("liberated").
Information on the fraction of lead-bearing grains that are included are summarized below:
Test Material
Phase I Residential Composite
FeMnPb Oxide
AV Slag
Oregon Gulch Tailings
Percent of Lead Mass
that is "Liberated"
92%
99%
80%
5%
As seen, most of the lead mass in the first three test materials is partly or entirely liberated.
In contrast, very few of the grains of galena observed in the Oregon Gulch tailings sample are
liberated, with nearly 95% of the grains (and hence the lead mass) occurring entirely within the
confines of slag particles.
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. Any animals that
appeared to be ill were also excluded. 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 8-11 kg. Animals were weighed every
three days during the course of the study. The group mean body weights over the course of
each study are shown in Figure 2-3. On average, animals gained about 0.3 to 0.4 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 the test groups covered in this report, there were no animals that
were judged by the principal investigator and the veterinary clinician to be seriously ill, and no
8
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FIGURE 2-3 BODY WEIGHTS OF TEST ANIMALS
PAMELA: STUDY 7
12
14
Study Day
PANELS: STUDY 8
1 control
2 PbAc 25
3 PbAc 75
4 Phase 125
5 Phase 175
6 Phase 1225
7Fe/Mn/Pb025
8Fe/Mn/PbO75
9Fe/Mn/PbO225
10 IV 100
X- 5 Control
- 6 Oral 25
7 Oral 75
8 AV Slag 25
9 AV Slag 75
10AV Slag 225
PANELC: STUDY 12
1 control
2 PbAc 25
3 PbAc 75
X- - 4 PbAc 225
11 Oregon Gulch 225
14
Study Day
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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 are
presented in Table 2-2. 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 of 1 ug/L) was less than 2 ug/L.
2.4 Dosing
The dosing protocols for exposing animals to lead in each of the three different studies are
shown in Tables 2-3, 2-4 and 2-5. The dose levels for lead acetate were based on experience
from previous investigations that showed that doses of 25-225 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 1, 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.
Most studies also included one or more dose groups exposed to lead acetate by intravenous
injection. The results of these studies are presented elsewhere.
10
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TABLE 2-2 TYPICAL FEED COMPOSITION3
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%
20.471 9 ppm
118.0608ppm
135. 3710 ppm
8. 1062 ppm
0.01 10 ppm
0.2075 ppm
0.3 196 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 .44 16 ppm
Nutritional values provided by Zeigler Bros., Inc.
11
-------
TABLE 2-3 DOSING PROTOCOL
STUDY 7
Group
1
2
3
4
5
6
7
8
9
Number
of
Animals
5
5
5
5
5
5
5
5
5
Dose
Material
Administered
None
Lead Acetate
Lead Acetate
Phase I Composite
Phase I Composite
Phase I Composite
Fe-Mn-Pb Oxide
Fe-Mn-Pb Oxide
Fe-Mn-Pb Oxide
Exposure
Route
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Oral
Lead Dose (ug Pb/kg-d)
Target
0
25
75
25
75
225
25
75
225
Actual3
27
74
26
78
233
25
76
231
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
-------
TABLE 2-4 DOSING PROTOCOL
STUDY 8
Group
5
6
7
8
9
19
Number
of
Animals
5
5
5
5
5
5
Dose
Material
Administered
None
Lead Acetate
Lead Acetate
AV Slag
AV Slag
AV Slag
Exposure
Route
Oral
Oral
Oral
Oral
Oral
Oral
Lead Dose (ug Pb/kg-d)
Target
0
25
75
25
75
225
Actual3
26
77
26
76
234
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.
13
-------
TABLE 2-5 DOSING PROTOCOL
STUDY 12
Group
1
2
3
4
11
Number
of
Animals
3
5
5
5
4
Dose
Material
Administered
None
Lead Acetate
Lead Acetate
Lead Acetate
Oregon Gulch Tailings
Exposure
Route
Oral
Oral
Oral
Oral
Oral
Lead Dose (ug Pb/kg-d)
Target
0
25
75
225
225
Actual3
27
78
239
232
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.
14
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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, 1, 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 Vacutainerฎ 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 90ฐC 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.
Bone
15
-------
The right femur of each animal was removed and defleshed, and dried at 100ฐC overnight. The
dried bones were then broken in half, placed in a muffle furnace and dry-ashed at 450ฐC 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) in
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.
16
-------
3.0 DATA ANALYSIS
3.1 Overview
Studies on the absorption of lead are often complicated because some biological responses to lead
exposure (especially blood lead level) 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 to either non-linear absorption and/or to non-linear biological response per unit adsorbed
dose. (Preliminary results from this program suggest the non-linear blood lead response is due
to due to non-linear lead binding by blood rather than non-linear gastrointestinal absorption).
In any event, 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 of Pb++ 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, internal maxima or minima, and 3) the general form of the equations had to
17
-------
be able 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 4- b-Dose
Exponential (EXP): Response = a 4- c-(l-exp(-d-Dose))
Combination (LIN+EXP): Response = a 4- 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 1 (see 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
Analytical Quality Assurance
A number of steps were taken throughout these studies to evaluate the quality of the results,
including blind analysis of numerous duplicate samples (to check reproducability), blind analysis
of "check samples" of blood provided by CDCP (to check accuracy), and independent analysis
of blood lead values by the CDCP (to check inter-laboratory performance). The results of these
analyses are presented in detail in Appendix 1, Section A (Study 7), Section B (Study 8) and
Section C (Study 12), and the results are summarized in Table 3-1.
18
-------
TABLE 3-1 SUMMARY OF QA RESULTS
Category
Correlation of EPA results
for duplicate samples of
blood
Correlation of EPA results
for duplicate samples of
bone and tissue
EPA results for CDCP
blood lead check samples
(ratio of mean of measured
to nominal value)
Correlation of inter-
laboratory analyses of
blood (EPA vs CDCP)
Parameter
Slope
R2
Slope
R2
Low Standard
Medium Standard
High Standard
Slope
R2
Study Number
7
0.97
0.99
0.96
0.99
1.07
0.88
0.97
0.74
0.91
8
0.97
0.99
1.06
0.98
1.25
0.73
0.94
0.91
0.99
12
0.96
0.99
1.16
0.997
0.79
0.95
1.04
0.98
0.98
19
-------
As seen, there is generally excellent agreement between duplicates analyses of both blood lead
and tissue lead, with best fit slopes and correlation coefficients (R2) both being near one.
Performance on check samples is also generally very good, with the mean ratios
(observed/nominal) mainly falling between 0.8 and 1.2. Results of blood samples analyzed by
CDCP tend to be slightly lower than those measured by the EPA laboratory, with the slopes of
the best fit linear lines through the data of 0.74-0.92. The reason for the apparent difference
in results between the EPA laboratory and the CDCP laboratory is not clear, but might be
related to differences in sample preparation techniques (CDCP was sent aliquots of whole blood
which they prepared and diluted independently). In any event, 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 RBA.
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 ACCESSฎ (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.
All spreadsheets used to manipulate the data and to perform calculations (see Appendix 1) were
validated by hand-checking random cells for accuracy.
20
-------
4.0 RESULTS
Detailed raw data for each animal in each of these studies are presented in Appendix 1 (Sections
A, B, and C). The following sections provide a summary of the results, focusing on mean
results for each dose group investigated.
4.1 Blood Lead vs Time
Figure 4-1 shows the group mean blood lead values as a function of time during the studies.
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. In animals given repeated oral
doses of lead acetate or test material, blood levels began to rise within 1-2 days, and tended to
plateau before the end of the study (day 15).
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 Appendices A to C, 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 except for the Oregon
Gulch sample in Study 12 (where only one dose was administered).
As seen, the dose response pattern is non-linear for both the soluble reference material (lead
acetate, abbreviated "PbAc"), and for each of the test materials. Dose response curves for Phase
I soil and Fe-Mn-Pb Oxide soil (Panel A) are rather similar to the curve for lead acetate, while
the response for AV Slag (panel B) and Oregon Gulch tailings (Panel C) are clearly lower than
for lead acetate.
Tissue Lead
The dose-response data for lead levels in bone, liver and kidney (measured at sacrifice on day
15) are detailed in Appendices A to C, and are shown graphically in Figures 4-3 through 4-5,
respectively.
As seen, all of these dose response curves for tissues are fit by linear equations. As was the
case for the blood lead AUC endpoint, the dose-response curves for Phase I soil and Fe-Mn-Pb
Oxide soil (Panel A) are rather similar to the curve for lead acetate, while the response for AV
Slag (panel B) and Oregon Gulch tailings (Panel C) are clearly lower than for lead acetate.
21
-------
FIGURE 4-1 GROUP MEAN BLOOD LEAD BY DAY
PANEL A: STUDY 7
^ 1 control | j
- B ~ 2 PbAc 25 ! I
- A 3 PbAc 75 ! ;
4 Phase i 25 | !
5 Phase I 75 I
B Phase I 225 ! j
7 FeVMn/PbO 25 | i
8 Fa/Mn/PbO 75 \ \
9 Fe/Mn/PbO225j j
10 IV 100
PANELS: STUDY 8
PANEL C: STUDY 12
I
!
i
1 *. vs -*ซ ^
9 -i- * *^ ** .***, * *" *, ซ
:! /'"' ,.-
4 i , , ' * -A- - . -A-
3} ' X
x^ ซ.~-Q"**a
* 1 control
ซ Q - 2 PbAc 25
- A - 3 PbAc 75
- * - 4 PbAc 225
- - 11 Oregon Gulch 225
2 4 6 8 10 12 14 16
Study Day
22
-------
FIGURE 4-2 BLOOD LEAD DOSE-RESPONSE
PAMELA: STUDY7
200 -
-I 140
ง 100
o 80 -
3 Rn
5 40 -
m
n .
Measured Data Points
r-1
H Best Fit Eqn for PbAc
Hy=6.2ป13B.6*(1-exD(-O.OW5X)}
K
i
I ซAVQ PbAc i
! 1 Avg Phase 1 |
Best l-it tqn tor HeMnHbO soil j j
/
/
. - * '^
N ^^^ ^
. ***
.
. T
'..i-
_^_- -Hr"
'
Best Fit Eqn tor Knase i BOH j
50
100 150 200
Lud OOM (ug Pb/kg-d)
250
300
PANELS: STUDY
I
|
3
/
^
/
/*\
/I
/ ,.-}-""""
8
Best Fit Eqn for PbAc
y=6.B+161.3'(1-exp(-Q.0045X))
...--'"
r
i
"^
Best Fit Eqn for t
Measure* Data Points
Avg Oral PbAc
A Avg AV Slag
--v-^'
W Slag
0 50 100 150
Lead Dose (ug Pb/kg-d)
I
I
200
250
300
V)
I
PANEL C: STUDY 12
Best Fit Eqn tor PbAc
y=6.8+129'(1-ซxp(-Q.0066X))
150
Lead Dose (us Pb/Kg-d)
200
250
300
23
-------
FIGURE 4-3 BONE LEAD DOSE-RESPONSE
PANEL A: STUDY?
14
12
10
S B H
- Best Fit Eqn fa
y_=1 0+0 048X
j :
j Best Fit Eqn for FeMnPbO Soil j , T . -,'1
PbAc
Stjfc^
_^^*^
. ^yf ""^
\
V
i^^
/
""' r-^^"
/
3hase I Soil
y=1.0+00298X
MeasLred Data Points
' Avo PbAc j-
Avo Phase I
vi 100 150 200 250 3C
Lปd Don (ug Pb/kg-d)
PANEL B: STUDY 8
ซ 5
n
S1 4
S1
50
100 150 200
Lead Dose (ug Pb/kg-d)
PANEL C: STUDY 12
i A
/
u/
/.$-
i
^
/^-L___ Best Fit Eqn for PbAc
*
j ^
--"
^\
Measured Data Points
1 -A
AA
Best Fit Eqn for AV Slag
v=1 1+0010X I
vg Oral PbAc j
vg AV Slag I
250
300
10 -j 1
9 -
i'.:
S1
i. 5-
j
-------
FIGURE 4-4 LIVER LEAD DOSE-RESPONSE
PAMELA: STUDY 7
450
400
350
300
250
200
150
100
50
~!Best Fit Eqn for FeMnPbO Soii
Jy=1S,3*1 <2X
! Best Fit Eon for PbAc
50
iBest Fit Eqn forPMase I Soil
Measurfed Data Points
100 150 200
Lซซd Dos* (ug Pb/kg-d)
BAvgPhasel
AAvfl FeMnPbO
250
300
PANELS: STUDY 8
250
200
150
100
50
Best Fit Eqn for PbAo
y=17.3+2.20X
HlR
Measured Data Points
B Avfl Oral PbAo j~
^ Avg AV Slag '
Best Fit Eqn for AV Slag
v=17 3*0 ?43X
50
100 150 200
Lead Dose (ug Pb/kg-d)
PANEL C: STUDY 12
250
300
Best Fit Eqn for PDAc
yซ14.7*1.05X
50
150
Lead Dose (uo/kfl-d)
200
250
300
25
-------
FIGURE 4-5 KIDNEY LEAD DOSE-RESPONSE
500
_ 450
ฃ 400
1 350
ซ 300
I 250
1 200
^ 150
| 100
* 50
0
PANEL A: STUDY 7
50
100 150 200
Lead Don (ug Pb/kg-d)
(Best Fit Eqn for FeMnPbO Soil i
Best Fit Eqn fo
v=15 1*1. 23X
\
. . '
|y=15.1*1.54X | r-sf-H !
rPbAc
\ ..-!"
\ -''' i ^-->^=r^
v.-- ^---r
_^ ^"^
___ j . " ^, "TlT" Measuried Data Points
^.yLs***^ \ \ i *AvoPbAc
X^i^f-*^^'
-"""^
Best Fit Eqn forPhase I Soil j *
v=15.1 + 1.13X ; AA
vg Phase I
vgFeMnPbO |
250
300
PANELS: STUDY8
300
r50'
a
3. 150
o
1
1
n .
I Best Fit Eqn for F
-|y=29.5+2.35X
\
\
/
A
/ .1
r"'
bAc
H
ซ/]
p /
X
f --
- 1 . . E-
1 IBest Fit Eqn (or AV Slag
y=29.5+0.242X
/
*;,..
Measuf
ed Data Points
Avg Oral PbAc
A Avg AV Slag
i*"
'
50
250
300
Lead Dose (ug Pb/kg-d)
PANEL C: STUDY 12
^ 250 -
ป 150 -
^^
^-**
Best Fit Eqn for PbAc
/10.4+1.02X
I
N^^.
w ^_>^-^*^^
^^
0 50 100
-
^-^
*
I -& * ""I
N
Measured Data Points
Avg PbAc
Avg Oregon Gulc
*
150 200
Lead Dote (ug/tcg-d)
250
300
26
-------
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
Phase I
Composite
0.71
0.92
0.91
0.62
Fe-Mn-Pb
Oxide
0.87
0.96
1.24
0.84
AV
Slag
0.20
0.11
0.10
0.18
Oregon
Gulch
0.06
0.05
0.04
0.004
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) depends 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.
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.
27
-------
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 ranee 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
Phase I
Composite
0.71 -0.82
0.71 -0.76
0.74
Fe-Mn-Pb
Oxide
0.87- 1.0
0.87 - 0.94
0.90
AV
Slag
0.13 -0.20
0.16 -0.20
0.18
Oregon
Gulch
0.03 - 0.06
0.05 - 0.06
0.06
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 and other similar solid media (slag, tailings),
as follows:
ABA
medium x
= ABA
soluble
RBA
medium x
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 soil-like site media
are calculated as follows:
ABA
medium x
= 50%-RBA,
medium x
Based on the RBA values shown above, the estimated absolute bioavailabilities in children for
the four site media tested at this site are as follows:
Absolute
Bioavailability
of Lead
Plausible Range
Preferred Range
Suggested Point Estimate
Test Material
Phase I
Composite
36%-41%
36%-38%
37%
Fe-Mn-Pb
Oxide
43% -51%
43% -47%
45%
AV
Slag
6%-10%
8%-10%
9%
Oregon
Gulch
2%-3%
2% -3%
3%
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
28
-------
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 and Doulls 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. Bioavailability 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 Bioavailabilitv 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
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.
30
-------
APPENDIX 1
DETAILED DATA AND CALCULATIONS FOR
USEPA SWINE BIOAVAILABILITY STUDY
PHASE II, EXPERIMENTS 7, 8 and 12
CALIFORNIA GULCH NPL SITE
TEST MATERIALS
Phase I Residential Soil Composite
Fe-Mn-Pb Oxide Soil
AV Smelter Slag sample
Oregon Gulch Tailings Sample
-------
APPENDIX 1
DETAILED DATA SUMMARY
CALIFORNIA GULCH SITE SAMPLES
1.0 OVERVIEW
Performance of the three studies covered in this report 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 Microsoft Excel spreadsheets that are available upon request from the administrative
record. These files are intended to allow detailed review and evaluation by outside parties of
all aspects of each study.
This Appendix provides detailed descriptions of the data reduction steps, along with printouts
of selected tables and graphs from the XLS files, organized into three sections, as follows:
Section
A
B
C
Study
7
8
12
Test Materials
Phase I Residential Composite Soil
Fe-Mn-Pb Oxide Soil
AV Slag
Oregon Gulch Tailings
Any additional details of interest to a reader can be found in the XLS spreadsheets.
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 1 and 2 of
Sections A, B, and C. Doses which required adjustment are shown by a heavy black box
outlining the value in Table 1 in each section.
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 3 of Sections
A, B, and C. 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 3 in each section.
Figures 1 to 3 in each section plot the results for individual animals organized by group and by
day. Figure 4 of each section plots the mean blood lead value for each dosing group by day.
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 each section in Table 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 in study 8 or 12 (Tables
B-5 and C-5), and two values were excluded in study 7 (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(di 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 6 in each section. 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 7 in each section.
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 ฑ20% (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
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
doses), 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 for each study, 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.
-------
Curve Fit Results
For each section, Table 8 lists the data used to fit these curves, indicating which endpoints were
excluded as outliers and why, and Table 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 7 and greater, found at the end of each section. 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 10 in each section.
5.0 QUALITY ASSURANCE DATA
A number of steps were taken throughout the 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, with figures and tables presented in Sections A, B, and C.
Duplicates
Duplicate samples were prepared and analyzed for about 5 % of all samples generated during the
study. In each section, Table 11 lists the first and second values for blood, liver, kidney, and
bone. The results are shown in Figure 5 of each section.
Standards
The Centers for Disease Control and Prevention (CDCP) provide 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 each section, Table 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 6.
Interlaboratorv 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.
In each section, the data are presented in Table 13, and the results are plotted in Figure 6.
-------
SECTION A
STUDY 7
Phase I Residential Soil Composite
FeMePb Oxide
-------
TABLE A-1 BODY WEIGHTS AND ADMINISTERED DOSES, BY DAY*
Body weights ปซ mcnurad on d*ys -1,2, S, 6,11,14. Weights for oth*f diys BB BsHmated, bisad on Snear N-twpDlaBon bปt,y**n
Svwie Stujfy Phase * Eip
718
735
743
2 709
2 74!
1 750
2 755
3 711
3 715
3 718
3 747
3 731
4 712
4 736
4 740
4 753
6 702
5 708
5 728
5 739
5 756
8 723
a 725
8 732
6 737
7 713
7 73D
7 736
7 741
ป 733
8 742
3 746
8 749
8 751
9 719
9 721
9 72S
9 744
9 745
10 722
10 724
10 734
H 754
8W ygPb
(kg) p.rdry
8 0
10.5 0
9.9 0
8.8 0
10.8 1!
11.5 0
11.1 0
10.8 0
9 8
10.7 0
9.4 0
99 0
104 0
12.2 0
9.1 0
11 0
8.3 0
113 0
12.1 0
8.9 0
10-5 0
10.2 0
12 D
9.5 0
8.7 0
9.4 0
9.5 0
113 0
9.1 0
96 0
102 0
11.2 0
11.6 0
10.6 0
10.1 0
123 0
9.2 0
9.3 0
12.4 0
7.8 0
tO.4 0
12 0
OayO
BW ugPb
(la) Pซdซy
82 a
10,9 0
10.2 0
8.7 290
11.2 280
11.9 290
11.5 230
11.3 839
97 839
11.1 839
9.7 839
10.2 839
106 292
12,3 292
9.2 292
11.3 292
8.5 842
11.5 842
12,4 842
92 842
10.9 842
10.2 2558
12.0 2551
9 7 2iS6
9.1 2S5ซ
9.8 268
98 268
11.5 266
9.5 268
10.5 849
91 949
10.3 948
11,6 949
11.9 849
11.1 2543
10.3 2543
12.5 2543
8.6 2543
9.3 2543
12.8 1172
82 1172
10.7 1172
12* 1172
0ซy1
EW ug Pb
M) mrmy
9.4 0
113 0
10.S 0
9* 289
69 289
11.4 280
12.3 280
12.0 290
11.7 839
103 939
11.5 839
10.0 839
10.8 839
10.7 282
12.5 282
9.3 282
11.7 282
8.7 842
11.8 642
12.9 842
9.4 842
11.4 642
10.3 2558
12.1 255$
10.0 2558
8.5 2558
10,2 268
13.2 268
11.7 268
10,0 268
11.0 848
9.6 84G
10.5 84G
12.1 848
12.3 341
11.5 2543
10.5 2543
12.8 2543
10.1 2543
9.3 2543
12.9 1172
8.6 1172
11.0 1172
12.8 1172
BW ugPb
g Pb
12.0 0
13.4 0
11.6 0
11.0 315
9.7 315
13.4 315
14.7 315
13,4 315
12.1 945
14,3 945
12.5 945
12.7 945
10.8 314
12.4 314
13.5 314
11.2 314
10.9 960
12.7 960
14.1 960
10.7 960
12.8 960
12.7 2900
12.2 2900
13.6 2900
121 2900
1 1 .4 2900
128 325
126 325
126 325
135 325
122 325
13.7 1036
120 1036
134 1036
14.3 1036
15,0 1036
13,5 2970
120 2970
14.8 2970
12.1 2870
11-1 2970
14.8 1371
10.2 1371
13.1 1371
13.8 1371
BW ygPb
1 ฃ.24 0
12.48 0
1396 0
12.3 0
11.16 315
98 315
13.82 315
15,26 315
13.76 315
12.4 945
14,96 945
12 82 945
13,16 945
11.16 31
12.98 31
13.58 31
11.56 31
13.78 31
11.3 960
12.5S 960
14.3 960
10,92 960
13.06 960
12.9 | 1455
12.58 2800
13.92 2900
12.7 2900
11.39 2900
1328 325
1286 325
12.82 325
1392 325
12.58 325
1426 1035
12.34 1036
13.98 1036
14.74 1036
15.3 1036
13.75 2870
12.1S 2970
I4S 2870
12,36 2970
11.4 2870
15.22 1371
1034 1371
13,64 1371
13.7 1371
[ 5575
8W ug Pb
15.7 0
12.9 0
14.6 0
12.8 0
11.6 339
8.9 339
139 339
15.5 339
14.1 33ป
14.2 1017
12.6 1017
15.2 1017
13.0 1017
13.3 1017
11.2 340
13.1 340
13.6 340
11.7 340
13.8 340
11.7 1009
13.0 1009
14.8 1009
11.1 1009
13.4 1009
13.5 | 4531
12.7 3081
14.6 3081
13.1 3081
11.7 3081
13.6 352
13.4 352
13.2 3S2
14.0 352
13.0 352
14.5 1134
12.5 1134
14.1 1134
15.0 1134
15.6 1134
14.3 3127
12.9 3127
15J 3127
12.9 3127
11.6 3127
157 1483
11.0 1463
13.7 1463
13.9 1463
Day 18
BvV ugPb
162 0
11-3 0
13-2 0
16.3 0
13.5 0
10.3 339
8.9 339
140 339
15.7 339
14.4 339
14.3 1017
12.8 1017
15.3 1017
13.1 1017
13.5 1017
11,2 340
13.3 340
13.7 340
11,7 340
13.9 340
12.0 1009
133 1009
14.9 1009
112 1009
13.7 1008
14.0 3091
12.8 3091
153 3091
13* 3081
1 2.1 3081
1 3.9 352
13.7 352
14.3 352
133 352
14.8 1134
12.7 1134
141 1134
15.4 1134
16.0 1134
14,7 3127
13.8 3127
15.S 3127
13.5 3127
12.3 3127
16.1 1483
11.7 1483
13.8 1463
14.1 1463
Day 11
BW ugPb
16.74 0
12.14 0
13.6 0
15.92 0
14.04 0
1Q.62 338
SSS 339
14.08 339
15.86 339
14.34 1017
U.02 1017
15.54 1017
13.29 1017
13.62 1017
11.16 340
13.48 340
13.8 340
11.82 340
13.9 340
12.36 1009
13.58 1009
15.18 1009
11.34 1009
1406 1009
14.62 3081
12.99 3091
16 3391
13.76 3091
14.38 352
14.1 352
14,48 352
13.94 352
15,08 134
12.92 134
142 134
16.88 134
16.3 134
15.24 3127
14.28 3127
16.4 3127
14.04 3127
12.63 3127
18.58 1463
12.44 1463
13.82 1463
14.24 1463
Day 12
BW ug Pb
16.7 0
12.6 3
14.1 0
16.6 0
14.7 0
113 346
94 346
149 346
166 346
15.0 1038
13.5 1036
182 1039
11.1 1036
14.4 1038
12,0 346
144 346
14.7 346
124 346
14.4 346
13.1 1073
14.3 1073
155 1073
12.2 1073
14.6 1073
14.7 3365
135 3365
16.2 3365
14.3 3365
15.0 381
14.9 381
15.3 381
148 381
18.1 1187
13.6 1187
14.6 1187
166 1187
17.0 1187
159 3493
148 34i3
169 3493
14.7 3493
133 3493
17.3 1568
12.8 1566
14.1 1566
15.0 1566
Day 13
BW ugPb
ซ.? 0
13.1 0
14.5 0
17.2 0
15.3 0
12.0 343
9.7 34J
15.7 348
17.4 348
15.7 1036
14.0 1039
16.9 1038
15.0 1039
15,2 1038
12.9 346
15.3 348
15.5 346
12.8 346
149 346
13.9 1073
15.0 1073
16.7 1073
13.1 1073
15.5 1073
14.8 3365
14.1 3365
164 3365
148 9365
15.9 381
15.7 391
154 391
16.2 381
153 381
17.1 1197
14.3 1167
16.0 1187
17.4 1187
1?.ซ 1187
185 3493
15.3 3493
17.6 3493
15.3 3493
14.0 3483
18.0 1568
13.2 1566
14.3 1566
15.7 1566
Day 14
BW ugPti
19.66 0
13.62 0
15 0
1792 0
15,82 0
1284 348
10.12 346
1856 346
18.2 345
18,38 1038
14.52 1031
1752 10J8
1564 1039
16.02 1038
13.62 346
18.22 346
18.38 346
1346 346
14.72 1073
15,74 1073
17.43 1073
14.04 1073
16.28 107S
14,9 3365
14.64 3365
16.54 3365
16.38 3365
13.96 3365
16.8 381
16.36 381
16.08 381
17.02 381
16.02 391
18.14 1187
14.92 1187
15.34 1167
18.34 1187
18.62 1187
172 3493
ISM 3493
18 3493
1598 3493
1462 3493
18.7 1568
1362 1566
1458 1566
1649 156B
Day 15
BW ugPb
166 0
14,1 0
155 0
185 0
16,5 0
133 0
105 0
174 0
18.0 0
17.1 0
15.0 0
19.2 0
18.7 0
169 a
14.7 0
17.1 0
17.2 0
14.0 0
15.5 0
16.5 0
16.2 0
14.9 0
17.0 0
15.0 0
15.2 0
18.7 0
15.9 0
14.5 0
17-7 0
17.0 0
16.7 0
17.8 0
16.7 0
19.2 0
15.6 0
15.7 0
18.2 0
18.3 0
17.8 0
16.4 0
18.5 0
166 0
15.3 0
19.4 0
14.0 0
141 0
17.2 0
Pig 717 h&md is consum* *i awl ing doss on days 4 wd 9. Thปsป dot*s mf* coniumad fta next morning and ar* adjusted for in ihe calculations
Pig 719 fwiปd ta consan* is wwiing tfos* on day 3. This dos* wis consumed fi* next morning ind is adjusted for in Bw c
-------
TABLE A-2
Body Weight Adjusted Doses
(Dose for OayBW for Day)
Swim Study Phase II Dtp 7
Group ID *
1 706
1 714
1 718
1 735
1 743
2 703
2 709
2 748
2 750
2 755
3 711
3 715
3 716
3 747
3 731
704
712
736
740
753
5 702
5 708
5 728
5 739
5 756
6 717
6 723
6 725
6 732
6 737
7 707
7 713
7 730
7 738
7 741
8 733
8 742
8 746
8 749
8 751
9 719
9 721
9 729
9 744
9 745
10 722
10 724
10 727
10 734
Day 0 Day 1
0 0
0 0
0 0
0 0
0 0
30,6 29.6
320 31.5
25.0 24.4
235 22.7
24.2 23.4
74.4 71.5
86.8 81.3
75.5 72.8
863 835
822 79.1
31.4 30.2
286 262
22.8 22.6
306 30,3
24.8 24.1
98.8 96.3
72.9 71.4
68.0 66.5
91.9 89.5
77.0 74.0
222.9 221.6
249.6 248.6
212.2 211.4
2624 2561
281 3 269.8
27.4 26.1
27.4 26.3
27.2 26.3
23.3 22.9
28.1 26.9
80.8 77.2
93.1 88.3
82.1 81.1
72.9 70.2
71.1 68.7
229,9 2207
246.8 242 1
202.9 1992
2636 2519
273.0 272.6
928 91.2
143.7 137.8
100.6 95.2
109.6 106.7
94.7 91 .8
Day 2 Day 3
0 0
0 0
0 0
0 0
0 0
28.6 30.0
31.1 34.2
23.8 25.3
22.0 23.2
22.6 24.3
68.7 71.6
76.4 81.8
70,3 73.8
80.9 840
76.2 80.5
29.1 30.5
25.8 27.0
22.3 23.2
30.0 30.6
234 24.3
93.9 968
700 74.1
65.1 68.7
87.1 91.9
71.3 75.7
220.3 2248
247.7 248.7
210.5 215.2
250.1 250.9
259.2 256.1
250 26.7
253 26.7
255 26.8
22.5 24.3
25.8 27.6
74.0 78.9
83.9 86.7
80.1 83.7
67.8 73.4
66.4 70.5
212.2 110.5
237.6 246,3
195,6 203,3
2412 251.1
272 2 280 4
89.6 95.9
132.3 139.1
90.4 96.3
1039 112.1
89 2 97 3
Day 4 Days
0 0
0 0
0 0
0 0
0 0
29.1 28.2
34.8 35.4
24.8 24.3
22.6 22.1
24.2 24.1
68.9 664
80.9 80.0
71.4 69.3
80.7 77.5
78.5 76.6
301 297
26.7 264
228 224
29.5 28.5
23.8 23.3
92.9 89.3
72.9 71 .7
67.3 66.0
90.1 88.4
74.6 73.6
110.2 324.0
240.2 232.2
211.3 207.6
242.1 233.9
243.6 232.2
26.0 25.2
25.6 24.5
256 245
23.7 232
26 9 26 1
76.3 73.9
85.1 81.8
79.5 75.6
71.9 70.5
67.9 65.5
322.6 209.3
238.4 230.9
197.3 191.6
244.0 237.4
269 8 260 0
93.6 91.4
133.5 128.4
93.5 90.8
110.1 108.3
96.6 96.0
0 0
0 0
0 0
0 0
0 0
29.0 28.6
36.5 36.1
24.4 23.6
22.2 21.4
24.3 23.6
68.3 67.5
80.7 78.4
68.8 65.9
782 75.9
76,9 74,3
30.2 29,1
26.5 25.3
23.5 233
29.0 28.0
24.0 234
91.2 88.0
78.0 75.9
690 88.1
91.7 89.8
78.5 75.0
231.7 228.2
245.2 237.8
219.9 214.0
245.3 236.5
253 6 254 2
26.5 25,4
26.3 25,8
26.3 25.8
24.8 241
27.6 267
78.5 75.5
88.2 86.0
80.2 770
752 727
70.8 89.2
2239 2198
2492 2467
206.1 203.3
252.3 246.1
275.3 267.7
94.8 92.4
135.4 1340
94.4 92.1
110.0 105.0
101.5 100.8
Day8 DayS
0 0
0 0
0 0
0 0
0 0
28.2 30.9
35.8 38.3
22.8 24.4
20.6 21.9
22.9 24.1
66.7 71.5
76.2 80.7
63.2 67.1
73.7 78.4
71.8 76.4
28.1 30.5
24.2 25.9
23.1 24.9
27.1 292
22.8 24.6
850 866
757 77.7
67.2 69.1
87.9 91.2
73.5 75.3
112.4 336.3
230.9 242.6
208.3 210.8
228.3 236.0
254.8 262.7
24.4 25,9
25.2 26.3
25.3 288
23.5 25.1
258 27.0
72.8 78.0
83.9 90.5
74.1 80.7
70.3 75,4
67.7 72,6
215.8 219.4
244,2 243,1
200,7 203,9
240.3 2420
260.5 264,4
90.1 93.3
132.6 132.5
89.9 94.0
100.5 106.8
100.1 105.4
0 0
0 0
0 0
0 0
31.4 31.9
38,0 37,8
24.2 241
21.8 21.4
236 231
71.2 70.9
79.4 78.1
66.3 654
77.5 76.6
75.5 74.7
30.5 30.5
256 252
24.8 24.6
29.0 28.8
24.8 245
84.0 81.6
78.0 743
67.8 56,5
90.1 89.0
73.5 71.8
2193 210.7
239.9 237.3
201.3 192.5
229.8 223.9
255.2 248.0
25.3 24.8
254 24.5
257 25.0
247 24.3
26,1 25,2
766 752
89.1 878
80.3 79.9
73.9 724
71.0 69.6
212.0 205.2
230.6 219,3
197.1 190,6
231.9 222,7
255.2 246.6
90.7 88.2
124.6 117.6
92.0 90.2
106.3 105.8
104.0 102.7
Day 12 Day 13
0 0
0 0
0 0
0 0
30.6 28.9
37.0 35.5
23.2 22.0
20.8 19.9
22.7 21.9
89.1 66.1
76.8 74.0
641 61.6
73.4 69.3
72.0 68.2
28.7 26.7
24.0 22.8
23.8 22.3
28,0 26.8
240 23.2
816 77.0
750 71.4
67.3 84.2
876 816
72.5 89.1
228-7 227.3
248.7 238.9
2Q8.0 205.7
235.3 2268
260.2 250.3
25.3 23.9
25.3 24.2
25.8 24.7
24,8 23.5
26.0 24.8
73.8 69.4
87.4 83.3
81.4 79.4
71.7 68.1
69.7 66.8
219.8 211.1
236.2 2281
206.3 200.0
237.8 2278
262.1 250,0
90.6 87.0
122.0 1184
93-7 91.0
111.3 109.4
104.5 99.5
0
0
0
0
27-4
34-2
20.9
19.0
21.2
63.4
71.5
59.2
65.5
64.8
25.0
21 3
21.1
25.7
22,4
72.9
68.2
61.4
78.4
660
225.8
229.9
203.5
218.8
241.1
226
23.3
23.7
22.4
23.8
65,5
796
77,4
64.7
64,1
203.1
220S
1941
2186
2389
837
115,0
88,5
107.6
95.0
0.0
0.0
0.0
0.0
29.5
35.2
23.8
21.7
23.3
69.1
78.9
67.6
77.4
75.2
29.4
25.3
232
28.7
23.8
87.7
73.6
668
88.3
73.3
223.0
241.2
208.8
2384
254.8
25.4
255
25.6
23.8
263
75.1
86.5
795
71.4
68.8
215.7
237.3
199.5
240.6
263.2
91.0
129.8
92.8
1076
98,6
0
0
0
0
26
26
26
25
28
7S
76
75
75
25
26
25
26
26
m
76
7S
7S
7ft '
22S
225
22S
22S
22S
26
26
26
28
28
7S
75
7S
75
76
225
225
225
225
225
100
100
118
141
95
87
93 107
92
105
90
103
100 98
117
101
93
115
95 104
117
86
89
118
98 104
99
107
93
108
113 104
101
102
103
95
105 101
100
115
106
95
92 102
96
105
89
107
117 103
91
130
93
108
99 104
-------
S>*ป Shrfy Ptau II Exp 7
TABLE A - 3 RAW AND ADJUSTED BLOOD LEAD DATA
PHASE II EXPERIMENT 7
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
8-970124
8-970163
8-970167
8-970153
8-970155
8-970141
8-970158
8-970132
8-970120
8-970140
8-970172
8-970129
8-970136
8-970138
8-970145
8-970123
8-970157
8-970133
8-970147
8-970171
8-970152
8-970135
8-970121
8-970154
8-970161
8-970131
8-970148
8-970130
8-970142
8-970174
8-970137
8-970156
8-970159
8-970127
8-970166
8-970144
8-970149
8-970146
8-970165
8-970170
8-970169
8-9701 68
8-970164
8-970122
8-970150
8-970125
8-970160
8-970173
8-970151
8-970214
8-970229
8-970181
8-970213
8-970179
8-970222
8-970219
8-970193
8-970205
8-970189
8-970226
8-970224
8-970227
8-970202
8-970200
8-970216
8-970209
8-970218
8-970188
8-970183
8-970217
8-970221
8-970204
8-970201
8-970185
8-970195
8-970206
8-970207
8-970177
8-970175
8-970187
8-970223
8-970215
8-970192
8-97021 1
8-970176
8-970197
8-970178
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
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
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase!
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
dosage qualifier lab result (uq/L) day
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 <
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 <
1
1.2
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
1
1
1
5.3
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
-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
0
0
0
0
source file
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951018
T951014
T951018
T951014
T951018
T951018
T951014
T951014
T951014
T951018
T951018
T951018
T951014
T951014
T951018
T951014
T951018
T951014
T951014
T951018
T951018
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951014
T951018
T951018
T951014
T951018
T951014
T951014
T951014
MATRIX Adjusted Value (uq/dL)' Notes
SLOOO
BLOOD
BLOOD
SLQOO
BLODD
SLOOD
SLOOO
BLOOD
SLQOO
BLOOD
BLOOD
SLOOO
BLODD
SLOOO
SLOOO
BLODD
8LQOO
B.LOOO
BLOOD
SLOOO
BLODD
SLOOO
SLOOO
BLODD
SLQQD
BLOOD
BLOOD
SLOOO
BLOOD
8LOOO
SLOOO
BLOOD
SLQOO
BLOOD
BLOOD
SLOOO
BLODD
81000
SLOQO
BLODD
8LOQO
BLOOD
BLOOD
SLOOO
BLOOD
8LOOD
SLOOO
BLOOD
8LOOD
BLODD
SLOOO
8LOQO
BLODD
SLOOO
BLOOD
BLOOD
SLOOO
BLODD
SLOOO
SLOOO
BLODD
SLOOO
BLOOD
BLOW)
SLQOO
BLOOD
SLOOD
SLOQO
BLODD
SLOOO
BLOOD
BLOOD
SLOOO
BLODD
8LOOO
SLOQO
BLOOD
8LQOO
BLOOD
BLODD
SLOOO
BLOOD
8LOOO
SLOOO
BLOOD
BLOOD
0.5
1.2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
5.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
Clotted
0.5
0.5
0.5
0.5
0.5
0.5
0.5
-------
S*ซป Study Ph>ป II bq> 7
pig number sample group material administered
dosage qualifier lab result (ug/L) day
MATRIX
Adjusted Value (ug/dL)' Notes
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
8-970212
8-970194
8-970180
8-970186
8-970225
8-970228
8-970220
8-970198
8-970208
8-970182
8-970191
8-970199
8-970277
8-970258
8-970268
8-970246
8-970283
8-970251
8-970242
8-970233
8-970262
B-97027B
8-970261
8-970248
8-970254
8-970231
8-970241
8-970260
8-970240
8-970237
8-970269
8-970253
8-970255
8-970282
8-970270
8-970230
8-970281
8-970252
8-970272
8-970247
8-970250
8-970271
8-970244
8-970276
8-970259
8-970265
8-970284
8-970234
8-970256
8-970279
8-970264
8-970257
8-970236
8-970263
8-970249
8-970267
8-970274
8-970273
8-970232
8-970239
8-970243
8-970266
8-970308
8-970329
8-970298
8-970323
8-970300
8-970291
8-970332
8-970293
8-970312
8-970311
8-970327
8-970328
8-970319
8-970335
8-970304
8-970317
8-970297
8-970316
8-970322
8-970303
8-970330
8-970310
8-970321
8-970290
8-970337
8-970301
8-970305
8-970286
8-970302
8
8
9
9
9
9
9
10
10
10
10
10
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
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
5
5
5
5
5
6
6
6
6
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase!
Phase 1
Phase i
75 <
75 <
225 <
225 <
225 <
225 <
225 <
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
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
1
1
1
1
1
1
1
1
1
1
1
2.6
1
1
1
1
1
1
1
1
1
1
1
1
1
1.4
1
1
1
1
1
1
1
1
1.2
1
1
1.8
2.6
3.1
1
1.3
1
1
1
1
1
1
1
1
1
1.6
1.4
2.9
3
2.2
2.2
11.5
11.8
15.9
7.7
8.9
1
1
1
1
1
1
1
1
1
1
1.2
1
2.3
2.5
1.8
1
1
1
1
1
1
2.3
2.8
1
1.2
5.8
6
4.7
2.3
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
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
T951018
T951014
T951014
T951014
T951018
T951018
T951018
T951014
T951014
T951014
T951014
T951014
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T95101B
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
BLOOD
SLQOO
BLOOO
BLOOD
8LQOO
BLOOO
BLOOD
SLQQO
BLOOD
SLQOO
aiooo
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOD
SLOOO
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
8LOQO
BLOOD
SLOOO
BLOOO
BLOOD
SLOOO
BLOOD
BLOOD
8LOOO
BLOOD
BLOOD
SLODO
BLOOD
BLOOD
BLOOD
SLQOO
81000
BLOCS)
SLOOP
BLOOO
BLOOD
8LOOO
BLOOD
SWOD
810.00
BLOOD
8LOOO
BLOOO
BLOOD
BLOOD
BLOOD
BLOOD
8L.OQD
BLOCS)
BLOOD
BLOOO
BLOOD
BLOOD
aiooo
BLOCS)
8LQOD
SLOOO
BLOOD
atooo
BLOCS)
BLOOD
8LOOO
BLOCS)
8LOOO
etooo
BLOOD
8LOOO
BLOOD
BLOOD
etooo
BLOOD
SLQOO
etooo
BLOOD
SLOOO
BLOOD
SIOOO
etooo
BLOCS)
BLOOD
SLOOO
BLOOD
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2.6
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.2
0.5
0.5
1.8
2.6
3.1
0.5
1.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.6
1.4
2.9
3
2.2
2.2
11.5
11.8
15.9
7.7
89
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.2
0.5
2.3
2.5
1.8
0.5
0.5
0.5
0.5
0.5
0.5
2.3
2.8
1
1.2
5.8
6
4.7
2.3
-------
Swim Study Phui II E*p 7
pig number sample group material administered
dosage qualifier lab result fug/L) day
e file
MATRIX
Adjusted Value (uq/dL)'
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
8-970288
8-970325
8-970338
8-970292
8-S70299
8-970309
8-970336
8-970285
8-970333
8-970295
8-970313
8-970339
8-970315
8-970294
8-970306
8-970289
8-970296
8-970326
8-970324
8-970307
8-970334
8-970389
8-970367
8-970394
8-970344
8-970350
8-970365
8-970340
8-970357
8-970351
8-970368
8-970363
8-970384
8-970354
8-970387
8-970378
8-970346
8-970385
8-970359
8-970366
8-970386
8-970393
8-970353
8-970383
8-970370
8-970391
8-970349
8-970355
8-970380
8-970382
8-970390
8-970377
8-970371
8-970388
8-970372
8-970342
8-970361
8-970362
8-970364
8-970345
8-970348
8-970352
8-970374
8-970341
8-970392
8-970356
8-970376
8-970379
8-970360
8-970375
8-970347
8-970413
8-970435
8-970401
8-970415
8-970424
8-970410
8-970440
8-970420
8-970421
8-970418
8-970434
8-970397
8-970395
8-970443
8-970402
8-970409
8-970419
8-970433
8-970405
8-970445
6
7
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
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
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
Phase 1
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/Mn PbO
Fe/Mn FtiO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/Mn PbO
Fe/MnPbO
Fe/Mn Pt>0
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
225
25
25 <
25 <
25 <
25
75
75 <
75 <
75 <
75
225
225
225
225
225
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
0 <
0 <
0 <
0 <
0 <
25 <
25 <
25 <
25 <
25
75 <
75
75
75
75
25 <
25 <
25 <
25 <
25 <
1.9
2.7
1
1
1
1
1.9
1
1
1
1.7
4.5
7.3
3.7
4.6
5.6
12.2
15
20.8
9.2
11.9
1
1
1
1
1
1
1
1
1
1
1
1
1.9
2.3
2.3
1
1
1
1
1
1.1
2
2.5
3
1.5
5.4
6
4.6
2.6
4.1
2.2
1.3
1
1
1
1.2
1
1
1
2
3.8
5.8
6.9
5.6
5.8
13.3
13.5
18.8
9.6
14.3
1
1
1
1
1
1
1
1
1
1.8
1
1.7
5.3
3
2.7
1
1
1
1
1
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
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951023
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951023
T951018
T951018
T951018
T951023
T951018
T951018
T951018
T951018
T951023
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951018
T951023
T951018
T951018
T951018
T951018
T951018
T951018
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
BLOOD
SLQOO
BIOQ0
BLOOD
8LOOO
BLOOD
BLOOD
SLOOD
BLOOD
stooo
81000
BLOOD
8LOOO
BLOOD
BLOOD
SLOOO
BLOOD
StOOD
8LOQO
BLOOD
SLOQO
SIOOD
BLOOD
SLOOO
81.0QO
BLOOD
SLOQO
BIOOD
BLOOD
8LOOO
BLOOD
8LQQ0
61000
BLODD
SLOQO
BLOOD
SLOOD
8LOOO
BLOOD
SLOOO
BLOOD
BLOOD
8LO.OO
BLOOD
BLOOD
SLOOQ
BLOOD
SLOOO
81000
BLOCS)
8LQOO
BLOOD
BLOOO
BLOOO
BLODD
8LOQO
81000
BLODD
SIQQO
BLOOD
SLOOO
SLOOO
BLOOD
SLQQ0
BLOOD
BLODD
BLOOD
BLOOD
SLOOD
auooo
BLQDD
BLOOD
BLOOD
BLOOD
BLODD
SLOOO
BLOOD
8LQOO
81000
BLOOD
8LQOO
BLOOD
BLOOD
SLOOO
BLOOD
8LOOO
81000
BLODD
SLQOO
BLOOO
BLOOD
1.9
2.7
0.5
0.5
0.5
1
1.9
0.5
0.5
0.5
1.7
4.5
7.3
3.7
4.6
5.6
12.2
15
20.8
9.2
11.9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.9
2.3
2.3
0.5
0.5
0.5
0.5
0.5
1.1
2
2.5
3
1.5
5.4
6
4.6
2.6
4.1
2.2
1.3
0.5
0.5
0.5
1.2
0.5
1
0.5
2
3.8
5.8
6.9
5.6
5.8
13.3
13.5
18.8
9.6
14.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.8
0.5
1.7
5.3
3
2.7
0.5
0.5
0.5
0.5
0.5
-------
Son Study PhD. II Ejp 7
pig number sample group material administered
dosage qualifier lab result (ug/L) day
source file
MATRIX
Adjusted Value (uq)dl)'
702
70S
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
8-970412
8-970446
8-970396
8-970398
8-970426
8-970422
8-970423
8-970436
8-970407
8-970428
8-970427
8-970408
8-970438
8-970400
8-970447
8-970411
8-970416
8-970441
8-970430
8-970439
8-970437
8-970417
8-970442
8-970448
8-970449
8-970431
8-970399
8-970425
8-970406
8-970444
8-970497
8-970456
8-970500
8-970484
8-970468
8-970480
8-970502
8-970450
8-970467
8-970492
8-970452
8-970462
8-970495
8-970461
8-970483
8-970486
8-970463
8-970475
8-970482
8-970471
8-970476
8-970479
8-970503
8-970487
8-970454
8-970499
8-970470
8-970474
8-970481
8-970469
8-970464
8-970491
8-970457
B-970496
8-970485
8-970501
8-970466
8-970459
8-970478
8-970477
8-970494
8-970455
8-970460
8-970504
8-970451
8-970465
8-970453
8-970472
8-970488
8-970498
8-970526
8-970528
8-970510
8-970537
8-970549
8-970530
8-970506
8-970518
8-970541
8-970539
8-970553
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
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
2
2
2
2
2
3
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/MnPbQ
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/Mn PbO
Fe/MnPbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
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
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
0 <
0 <
0 <
0
0 <
25
25 <
25
25
25
75
1.1
3
3.7
1.1
3.2
8.4
5.5
4.7
4.2
5.3
1.9
1
1.1
1
1
1.2
1.7
2.5
1
3.6
4
10.7
8.3
5.6
6.3
15.6
17.7
19.9
11.1
14.5
1
1
1
1
1
1
1
1
1
2
1.9
1.6
5.6
3.4
3.8
1
1.1
1
1
1
1.6
2.7
3.7
1.9
3
6.1
6.2
5.7
6.2
5.4
2
1
2.2
1
1
2
1.4
2.5
1.6
3
6.1
7.9
8.5
6.2
7.2
18.1
16.7
23.3
13.3
15.8
1
1
1
1.5
1
1.8
1
1
1.5
2.7
2.3
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
7
7
7
7
7
7
7
7
7
7
7
7
7
9
9
9
9
9
9
9
9
9
9
9
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
BLOOD
stooo
81000
BLOOD
BLOOD
BLOOD.
BLOOD
BLOOD
BLOOD
SLQQO
81.000
BLOD0
BLOOD
BLOOD
BLOOD
a LOGO
BLOOD
SLOOO
aiooo
BLOOD
SLQQO
8LOOD
BLOOD
8LOOO
BLOOD
SLOQO
BLOOD
BLOOD
BLOOD
BLOOD
BtOOD,
8LOOO
61000
BLOOD
SLOOO
8LOOD
. SLOOD
8LOOO
BLOOD
StQOO
aiooo
BLOOD
BLOOD
BLOOD
BLOOD
SLOQO
BLOOD
SLOOO
61000
BLOOD
8LQOO
BLOOD
BLOOD
BLOOD
BLOOD
StQOO
81000
BLOOD
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
8LOQO
aiooo
BLOOD
BLOOD
BLOOO
BLOOD
BLOOO
BLOOD
SLOOO
61OQO
BLOOD
SLQQO
8LOOO
BLOOD
BLOOD
BLODD
8U5QO
SLOOO
BLOOD
BLOOD
BLOOO
BLOOD
SLOOO
8LOOO
BLODD
BLOOD
BtOOD
BLOOD
1.1
3
3.7
1.1
3.2
8.4
5.5
4.7
4.2
5.3
1.9
0.5
1.1
0.5
1
1.2
1.7
2.5
0.5
3.6
4
10.7
8.3
5.6
6.3
15.6
17.7
19.9
11.1
14.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
2
1.9
1.6
5.6
3.4
3.8
0.5
1.1
0.5
0.5
0.5
1.6
2.7
3.7
1.9
3
6.1
6.2
5.7
6.2
5.4
2
0.5
2.2
0.5
0.5
2
1.4
2.5
1.6
3
6.1
7.9
8.5
6.2
7.2
18.1
16.7
23.3
13.3
15.8
0.5
0.5
0.5
1.5
0.5
1.8
0.5
1
1.5
2.7
2.3
-------
Swtw Study Phna II Exp 7
pig number
716
747
731
704
712
736
740
753
702
708
728
739
786
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
714
ample
8-970516
8-970557
8-970551
8-970532
8-970538
8-970521
8-970509
8-970558
8-970513
8-970507
8-970531
8-970559
8-970519
8-970523
8-970556
8-970529
8-970548
8-970534
8-970540
8-970546
8-970517
8-970550
8-970511
8-970520
8-970512
8-970525
8-970514
8-970542
8-970552
8-970524
8-970505
8-970554
8-970543
8-970535
8-970527
8-970508
8-970545
8-970515
8-970602
8-970578
8-970566
8-970608
8-970577
8-970560
8-970592
8-970594
8-970601
8-970574
8-970604
8-970580
8-970562
8-970600
8-970591
8-970584
8-970565
8-970571
8-970595
8-970589
8-970590
8-970599
8-970588
8-970581
8-97061 1
8-970607
8-970610
8-970563
8-970585
8-970572
8-970609
8-970593
8-970576
8-970605
8-970596
8-970598
8-970573
8-970568
8-970606
8-970582
8-970614
8-970575
8-970603
8-970561
8-970612
8-970597
8-970613
8-970570
8-970583
8-970564
8-970622
group
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
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
material administered
PbAc
PbAc
PbAc
Phase I
Phase!
Phase I
Phase!
Phase I
Phase I
Phase I ~
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase!
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/Mn Pt>O
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase I
Phase !
Phase I
Phase!
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase!
Phase!
Phase I
Phase I
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
dosage
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
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
0
qualifier lab resuft (ug/L)
6.5
4.2
5.8
1.5
1.9
< 1
2.1
1.3
2.6
4.3
3.9
2.1
3.5
1.8
7.1
6.3
6.1
6.9
3
< 1
3
< 1
2.2
3.6
2.5
3.4
2.4
4.1
6.5
9.5
10.1
6.7
6.9
20
21
24.2
12.5
17.9
1
1
1
1
1
1
1
1.1
2.2
2.7
1.4
< 1
14.4
24
3.7
< 1
< 1
< 1
< 1
< 1
2.6
3.1
2.1
3
3.4
4.8
6.8
5
4.8
6
1.5
1.2
2
< 1
1
2.8
1.9
1.5
2
4.4
7
6.8
10.5
7
9.3
16.2
16.5
21.9
12.1
10.7
< 1
day
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
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
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
8tooo
BLOOD
BLOOD
8LOOO
BLOOD
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
8LOQO
81000
SLOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LQOO
BLOOD
SLOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLQOO
BLOOD
BLOOO
BLOOD
BLOOD
etooo
BLOOO
BLOOD
8LQQO
BLOOD
BLOOO
BLOOO
B.L.OOO
BLODO
BLOOO
BLOOO
6LOOD
BLOOD
BLOOD
BLQOO
81000
BLQOt)
8LOOO
BLOOO
BLOOD
BLOOD
BLOOD
8LQOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOO
BLOOD
BU500
BLOOD
BLOOD
BLOOD
BLOOD
SLQOO
BLOOO
BLOOD
BLOOO
BLOCS*
BLOOD
8L.QOO
BLOOD
BLOOD
BLOOD
BLOOD
SLQOO
BLOOO
BLOOD
8LOOO
BLOOO
BLOOD
BLOOD
BLOOD
SWOO
BLOOD
BLOOO
BLOOO
6.5
4.2
5.8
1.5
1.9
0.5
2.1
1.3
2.6
4.3
3.9
2.1
3.5
1.8
7.1
6.3
6.1
6.9
3
0.5
3
0.5
2.2
3.6
2.5
3.4
2.4
4.1
6.5
9.5
10.1
6.7
6.9
20
21
24.2
12.5
17.9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.1
2.2
2.7
1.4
0.5
14.4
2.4
3.7
0.5
0.5
0.5
0.5
0.5
2.6
3.1
2.1
3
3.4
4.8
6.8
5
4.8
6
1.5
1.2
2
0.5
1
2.8
1.9
1.5
2
4.4
7
6.8
10.5
7
9.3
16.2
16.5
21.9
12.1
10.7
0.5
0.5
-------
Son Study Ptnu II Eซp 7
material administered
dosaqe qualifier lab result (ug/L) day
MATRIX
Adjusted Value (uq/dL)' Notes
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
. 713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
8-970626
8-970621
8-970666
8-970657
8-970642
8-970650
8-970656
8-970648
8-970625
8-970629
8-970643
8-970641
8-970630
8-970645
8-970633
8-970619
8-970627
8-970624
8-970618
8-970644
8-970640
8-970639
8-970652
8-970667
8-970651
8-970623
8-970616
8-970660
8-970654
8-970646
8-970634
8-970655
8-970638
8-970661
8-970631
8-970669
8-970647
6-970615
8-970649
8-970663
8-970637
8-970635
6-970668
6-970665
8-970617
8-970653
8-970658
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
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
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
1
1
1
1
1
2.1
3.3
2.9
2.1
12.9
4.9
4.2
1
1
1
1
2.6
3.7
3.4
3.5
4.5
3.3
6.4
10.2
7.9
6.8
5.1
1.5
1.4
3.3
1.1
27
3.6
3.5
4.3
3.8
6.5
9.4
10
10.8
8.4
8.1
17.9
16.7
23.3
13.1
11.3
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
T951023
T951023
T951101
T951101
T951023
T951018
T951101
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951023
T951 101
T951 101
T951101
T951023
T951023
T951 101
T951 101
T951023
T951023
T951 101
T951023
T951 101
T951023
T951 101
T951023
T951023
T951023
T951 101
T951023
T951023
T951 101
T951101
T951023
T951 101
T951101
T951023
BLOOD:
SLQ00
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LQOO
81000
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOQO
BLOOD
BLOOD
SLQQO
BLOOO
6L000
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
8LQOO
8LOOD
BLOOO
BLOOD
BLOOD
BLOOD
BLOOO
BLODb
8LOOO
BLOOO
6LOOO
BLOOD
BLOOD
SLOOO
BLOOD
BLOOD
8LOOO
BLOOO
BLOOO
BLOOD
0.5
0.5
0.5
0.5
0.5
0.5
2.1
3.3
2.9
2.1
12.9
4.9
4.2
0.5
0.5
0.5
0.5
2.6
3.7
3.4
3.5
4,5
3.3
6.4
10.2
7.9
6.8
5.1
1.5
1.4
3.3
1.1
2.7
3.6
3.5
4.3
3.8
6.5
9.4
10
10.8
8.4
8.1
17.9
16.7
23.3
13.1
11.3
Non-detects evaluated using 1/2 the quantitalion Brail; laboratory results (ug/L) converted to concentration in blood (ug/dL) by dividing by dilution factor of 1 dUL.
-------
Swine Study Phปe II Ext 7
TABLE A-4 BLOOD LEAD OUTLIERS
Flagged Data Points
lOutiiers
test target
material dosage
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
Phase 1 25
Phase 1 25
Phase 1 25
Phase 1 25
Phase 1 25
Phase 1 75
Phase 1 75
Phase 1 75
Phase 1 75
Phase 1 75
Phase 1 225
Phase 1 225
Phase 1 225
Phase 1 225
Phase 1 225
Fe/Mn/PbO 25
Fe/Mn/PbO 25
Fe/Mn/PbO 25
Fe/Mn/PbO 25
Fe/Mn/PbO 25
Fe/Mn/PbO 75
Fe/Mn/PbO 75
Fe/Mn/PbO 75
Fe/Mn/PbO 75
Fe/Mn/PbO 75
Fe/Mn/PbO 225
Fe/Mn/PbO 225
Fe/Mn/PbO 225
Fe/Mn/PbO 225
Fe/Mn/PbO 225
IV 100
IV 100
IV 100
IV 100
IV 100
Actual
Dose*
0.00
0.00
0.00
0.00
0.00
29.54
35.21
23.82
2166
23.35
69.07
78.87
67.65
77.43
75.18
29.36
25.29
23.17
28.74
23.81
87.72
73.55
66.81
88.29
73.29
222.95
241.21
208.81
238.42
254.82
25.37
25.47
25.65
23.80
26.30
75.08
86.46
79.50
71.40
68.77
215.68
237.34
199.45
240.58
263.25
91.02
129.79
92.85
107.56
98.61
group
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#
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
-4
0.5
0.5
1.2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.1
0.5
0.5
0.5
0.5
0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
{ 5,3 )
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
Missing
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2.6
1
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.2
0.5
0.5
1.8
2.6
3.1
0.5
1.3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.6
1.4
2.9
3
2.2
2.2
11.5
11.8
155
7.7
8.9
2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.2
0.5
2.3
2.5
1.8
0.5
0.5
0.5
0.5
0.5
0.5
2.3
2.8
1
1.2
5.8
6
4.7
2.3
1-9
2.7
0.5
0.5
0.5
1
1.9
0.5
0.5
0.5
1.7
4.5
7.3
3.7
4.6
5.6
12.2
15
20,8
9i
11.9
BLOOD
3
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.9
2.3
2.3
0.5
0.5
0.5
0.5
0.5
1.1
2
2.5
3
1.5
5.4
6
4.6
2.6
4.1
2.2
1.3
0.5
0.5
0.5
1.2
0.5
1
0.5
2
3.8
5.8
6.9
5.6
5.8
13.3
13.5
18.8
9.6
14.3
LEAD (ug/dL) BY DAY
5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.8
OS
1.7
53
3
2.7
0.5
0.5
0.5
0.5
0.5
1.1
3
3.7
1.1
3.2
8.4
5.5
4.7
4.2
5.3
1.9
0.5
1.1
0.5
1
1.2
1.7
2.5
0.5
3.6
4
10.7
8.3
5.6
6.3
15.6
17.7
19.9
11.1
14.5
7
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
2
1.9
1.6
56
3.4
3.8
0.5
1.1
0.5
0.5
0.5
1.6
2.7
3.7
1.9
3
6.1 ^
6.2
5.7
6.2
54
2
0.5
2.2
0.5
0.5
2
1.4
2.5
1.6
3
6.1
7.9
8.5
6.2
7.2
18.1
16.7
23.3
13.3
15.8
9
0.5
0.5
0.5
1.5
0.5
1.8
0.5
1
1.5
2.7
23
3.5
6.5
4.2
5.8
1.5
1.9
0.5
2.1
1.3
26
4.3
3.9
2.1
3.5
m&m
7.1
6.3
6.1
6.9
3
0.5
3
0.5
2.2
3.6
2.5
3.4
2.4
4.1
6.5
9.5
10.1
6.7
6.9
20
21
24.2
12.5
17.9
12
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.1
2.2
2.7
1.4
0,5
14.4
2,4
3.7
0.5
0.5
0.5
0.5
0.5
2.6
3.1
2.1
3
3.4
4.8
6.8
5
4.8
6
1.5
1.2
2
0.5
1
2.8
1.9
1.5
2
4.4
7
6.8
10.5
7
9.3
16.2
16.5
21,9
12.1
10.7
15
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2.1
3.3
2.9
2,1
12.&
4.9
4.2
0.5
0.5
0.5
0.5
2.6
3.7
3.4
3.5
4.5
3.3
6.4
10.2
7.9
6.8
6,1
1.5
1.4
3.3
1.1
2.7
3.6
3.5
4.3
3.8
!;*SปiP
9.4
10
10.8
8.4
8.1
17.9
16.7
23,a
13.1
11.3
* Average Time and Weight-Adjusted Dose for Each Pig
Missing values are a result of clotting in the whole blood, preventing accurate preparation of diluted samples.
-------
Swine Study Phase II Exp 7
TABLE A-5 RATIONALE FOR PbB OUTLIER DECISIONS
OUTLIER IDENTIFICATION
1 Day 0
Group 2
Pig # 750
2 Day 9
Group 6
Pig #717
RATIONALE
Based on comparison with responses by other
animals in this group on this day, the response of
animal 750 is significantly higher. In addition, it
is significantly higher than the value obseved in
the same animal one day earlier. Therefore, this
value is excluded and replaced with an interpolated
value of 0.5 ug/dL.
Based on comparison with responses by other
animals in this group on this day, the response of
animal 717 is significantly lower. In addition, it
is significantly lower than the value obseved in
the same animal one day earlier. Therefore, this
value is excluded and replaced with an interpolated
value of 5.45 ug/dL.
-------
Swine Study Phase II Exp 7
TABLE A-6 Area Under Curve Determinations
Calculated using interpolated values for missing or excluded data as noted in Table A-5
AUC (ug/dL-days) For Time Span Shown
group
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
g
9
10
10
10
10
10
pig#
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
0-1
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
o.gs
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.85
0.50
0.50
1.15
1.55
1.80
0.50
o.go
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
1.05
o.gs
1.70
1.75
1.35
1.35
6.00
6.15
8.20
4.10
5.75
1-2
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.85
0.50
1.40
i.gs
1.15
0.50
0.50
0.50
0.50
0.50
0.50
1.40
2.00
0.75
0.85
3.80
4.30
3.90
1.40
1.60
1.60
0.50
0.50
0.50
0.75
1.20
0.50
0.50
0.50
1.65
2.95
5.10
3.35
3.40
3.90
11.85
13.40
18.35
8.45
10.40
2-3
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.85
0.50
2.10
2.40
2.05
0.50
0.50
0.50
0.50
0.50
0.80
2.15
2.65
2.00
1.35
5.60
6.00
4.65
2.45
3.00
2.45
o.go
0.50
0.50
0.75
1.55
0.50
0.75
0.50
1.85
4.15
6.55
5.30
5.10
5.70
12.75
14.25
19.80
9.40
13.10
3-5
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
2.30
1.00
2.20
7.20
5.30
5.00
1.00
1.00
1.00
1.00
1.00
2.20
5.00
6.20
4.10
4.70
13.80
11.50
g.so
6.80
g.40
4.10
1.80
1.60
1.00
1.50
2.40
2.20
3.50
1.00
5.60
7.80
16.50
15.20
11.20
12.10
28.go
31.20
38.70
20.70
28.80
5-7
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.50
1.00
3.80
2.40
3.30
io.go
6.40
6.50
1.00
1.60
1.00
1.00
1.00
2.70
5.70
7.40
3.00
6.20
14.50
11.70
10.40
10.40
10.70
s.go
1.00
3.30
1.00
1.50
3.20
3.10
5.00
2.10
6.60
10.10
18.60
16.80
11.80
13.50
33.70
34.40
43.20
24.40
30.30
7-9
1.00
1.00
1.00
2.00
1.00
2.30
1.00
2.00
2.00
4.70
4.20
5.10
12.10
7.60
g.eo
2.00
3.00
1.00
2.60
1.80
4.20
7.00
7.60
4.00
6.50
11.55
13.30
12.00
12.30
12.30
5.00
1.00
5.20
1.00
2.70
5.60
s.go
s.go
4.00
7.10
12.60
17.40
18.60
i2.go
14.10
38.10
37.70
47.50
25.80
33.70
g-12
1.50
1.50
1.50
3.00
1.50
3.45
1.50
3.15
5.55
8.10
5.55
6.00
31.35
9.90
14.25
3.00
3.60
1.50
s.go
2.70
7.80
11.10
9.00
7.65
10.35
15.38
20.85
16.95
16.35
19.35
6.75
2.55
7.50
1.50
4.80
g.eo
6.60
7.35
6.60
12.75
20.25
24.45
30.90
20.55
24.30
54.30
56.25
eg. 15
36.90
42.90
12-15
1.50
1.50
1.50
1.50
1.50
1.50
1.50
2.40
6.45
g.oo
6.45
3.90
40.95
10.95
11.85
1.50
1.50
1.50
1.50
4.65
9.45
g.75
8.40
11.25
10.05
16.80
25.50
19.35
17.40
16.65
4.50
s.go
7.95
2.40
5.55
9.60
8.10
8.70
8.70
16.35
24.60
25.20
31 .95
23.10
26.10
51.15
49.80
67.80
37.80
33.00
AUC Total
(ug/dL-days)
7.50
7.50
7.50
10.00
7.50
10.75
7.50
11.55
17.50
2g.40
21.80
22.00
106.50
45.45
50.90
10.00
12.20
7.50
11.50
12.65
28.15
42.60
44.10
33.25
40.50
82.58
g4.70
78.35
67.60
7350
28.80
12.15
27.05
8.40
18.05
33.65
25.40
32.20
23.go
52. gs
83.40
115.50
123.85
89.40
101.05
236.75
243.15
312.70
167.55
197.95
-------
SWIM Study Phu* II Exp 7
TABLE A-7 TISSUE LEAD DATA
PHASE II EXPERIMENT 7
pig number sample group material administered
dosage qualifier lab result (ug/L) day
source file
MATRIX
Adjusted Value*
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
754
706
714
718
735
743
703
709
748
750
755
711
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
8-970839
8-970854
8-970833
8-970871
8-970863
8-970832
8-970872
8-970840
8-970870
8-970868
8-970825
8-970845
8-970862
8-970842
8-970874
8-970837
8-970841
8-970869
8-970846
8-970875
8-970849
8-970873
8-970865
8-970824
8-970848
8-970876
8-970859
8-970857
8-970828
8-970831
8-970861
8-970853
8-970836
8-970834
8-970860
8-970864
8-970852
8-970838
8-970856
8-970850
8-970847
8-970843
8-970827
8-970826
8-970866
8-970855
8-970851
8-970829
8-970835
8-970858
8-970785
8-970797
8-970821
8-970814
8-970772
8-970786
8-970817
8-970823
8-970791
8-970799
8-970787
8-970805
8-970800
8-970782
8-970793
8-970812
8-970778
8-970775
8-970774
8-970819
8-970822
8-970776
8-970813
8-970792
8-970794
8-970779
8-970795
8-970803
8-970781
8-970777
8-970806
8-970807
8-970801
8-970789
8-970788
8-970773
8-970780
8-970811
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
a
8
9
9
9
9
9
10
10
10
10
10
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
control
control
control
control
control
PbAc
PbAc -
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Phase 1
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
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
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
2
1.5
2
1.1
2.9
2
1.6
3.8
6.6
8
9.6
6.9
30.3
12.2
10.1
2.4
3.6
7.1
2
2.7
6.5
6.1
10.1
6.3
5.2
17
18.9
14.3
15.6
15.2
11.2
4
8.9
3.4
4
8.1
6.4
7.8
9.4
12
20.5
16.6
28.2
23.4
23.6
105
84
86
113
84.2
2
2
2
2
2
2.9
2
2.9
16.2
8.3
12
5.7
59.5
14.3
10.4
2
3.9
2.7
3.5
4.6
13.8
8.9
6.7
12.4
7.4
28.6
30
28.7
23.2
21.6
5.4
3.7
6.6
3.8
7.7
12.9
12.5
14.8
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
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
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
FEMUH
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUH
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMW . .
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
KIDNEY
KIDNEY
KfDNEY
KtDNEY
MONEY
KIDNEY
MONEY
KfDNEY
KtDNEY
MONEY
MONEY
KปN6Y
KIDNEY
KfDNEY
MONEY
KfDNEY
KIDNEY
MONEY
KIDNEY
MONEY
MONEY
KIDNEY
KIDNEY
KtDNEY
KIDNEY
MONEY
KIDNEY
KIDNEY
MONEY
KIDNEY
MONEY
KtDNEY
KIDNEY
MONEY
KIDNEY
KIDNEY
MONEY
KIDNEY
0.5
0.75
0.5
0.55
1.45
0.5
0.8
1.9
3.3
4
4.8
3.45
15.15
6.1
5.05
1.2
1.8
3.55
0.5
1.35
3.25
3.05
5.05
3.15
2.6
8.5
9.45
7.15
7.8
7.6
5.6
2
4.45
1.7
2
4.05
3.2
3.9
4.7
6
10.25
8.3
14.1
11.7
11.8
52.5
42
43
56.5
42.1
10
10
10
10
10
29
10
29
162
83
120
57
595
143
104
10
39
27
35
46
138
89
67
124
74
286
300
287
232
216
54
37
66
38
77
129
125
148
-------
Son Study Ptau II Eq> 7
751
719
721
729
744
745
722
724
727
734
706
714
718
735
743
703
709
748
750
755
71 1
715
716
747
731
704
712
736
740
753
702
708
728
739
756
717
723
725
732
737
707
713
730
738
741
733
742
746
749
751
719
721
729
744
745
722
724
727
734
8-970808
8-970818
8-970816
8-970771
8-970820
8-970802
8-970804
8-970815
8-970783
8-970810
S-970762
8-970752
8-970729
8-970755
8-970720
8-970724
8-970736
8-970753
8-970738
8-970721
8-970726
8-970766
8-970718
8-970742
8-970731
8-970735
8-970733
8-970744
8-970746
8-970719
8-970749
8-970722
8-970759
8-970723
8-970758
8-970756
8-970734
8-970747
8-970727
8-970751
8-970757
8-970745
8-970750
8-970743
8-970754
8-970760
8-970728
8-970748
8-970761
8-970730
8-970737
8-970740
8-970732
8-970764
8-970769
8-970725
8-970767
8-970763
8-970770
8
9
9
9
9
9
10
10
10
10
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
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/MnPbO
Fe/Mn PbO
IV
IV
IV
IV
control
control
control
control
control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Phase!
Phase I
Phase I
Phase!
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase I
Phase!
Phase I
Phase I
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
IV
IV
IV
IV
75
225
225
225
225
225
100
100
100
100
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
20
35.6
31.4
49.6
39.9
43.6
124
126
107
106
124
< 2
< 2
< 2
< 2
2.7
3
4.5
13.4
11.3
9.2
8.1
68.1
21.2
10.7
2
6.9
4.2
2.7
7.3
12.6
9.8
9.8
10.1
8
33.8
37.4
36.5
21
29.5
6.5
4.2
5.2
3.5
5.8
8.5
11.7
8.8
17.7
24.2
45.6
25.8
56.6
30
39.7
154
259
152
169
"y
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
source file
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106K
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
T960106L
MATRIX
KIQNEY
KiDNEY
KIDNEY
KIDNEY
(CONEY
MONEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
WDNEY
OVER
LIVER
UVER
UVER
LIVER
OVER
LIVER
UVER
LIVER
LIVER
UVER
L1VER
UVER
UVER
WES
UVER
UVER
JJVER
UVER.
UVER
LIVER
UVER
LIVER
UVER
UVER
LIVER
UVER
UVER
UVER
LIVER
UVER
UVER
LIVER
LIVER
UVER
LIVER
UVER
UVER
LIVER
UVER
LIVER
UVER
UVER
UVER
LIVER
UVER
LIVER
UVER
UVER
Adjusted Value1 Notes
200
356
314
496
399
436
1240
1260
1070
1060
1240
10
10
10
10
27
30
45
134
113
92
81
681
212
107
20
69
42
27
73
126
98
98
101
80
338
374
365
210
295
65
42
52
35
58
85
117
88
177
242
456
258
566
300
397
1540
2590
1520
1690
1480
Non-detects evaluated using 1/2 the quantitation limit. Laboratory results (ug/L) converted to tssue concentrations by dviding by sample dilution (actors of
0.1 kg/L (Iver, kidney) or 2 g/L (ashed bone). Final units are ug Pb/kg wet weight (liver, kidney) or ug Pb/g ashed bone (femur).
-------
Swine Study Phase II Exp 7
TABLE A-8 SUMMARY OF ENDPOINT OUTLIERS
J Selected Outliers
test target Actual
material dosage Dose* group pig#
control 0 0.00 1 706
control 0 0.00 1 714
control 0 0.00 1 718
control 0 0.00 1 735
control 0 0.00 1 743
PbAc 25 29.54 2 703
PbAc 25 35.21 2 709
PbAc 25 23.82 2 748
PbAc 25 21.66 2 750
PbAc 25 23.35 2 755
PbAc 75 69.07 3 711
PbAc 75 78.87 3 715
PbAc 75 67.65 3 716
PbAc 75 77.43 3 747
PbAc 75 75.18 3 731
Phase I 25 29.36 4 704
Phase I 25 25.29 4 712
Phase 1 25 23.17 4 736
Phase I 25 28.74 4 740
Phase I 25 23.81 4 753
Phase I 75 87.72 5 702
Phase I 75 73.55 5 708
Phase I 75 66.81 5 728
Phase I 75 88.29 5 739
Phase I 75 73.29 5 756
Phase I 225 222.95 6 717
Phase I 225 241.21 6 723
Phase! 225 208.81 6 725
Phase I 225 238.42 6 732
Phase I 225 254.82 6 737
Fe/Mn/PbO 25 25.37 7 707
Fe/Mn/PbO 25 25.47 7 713
Fe/Mn/PbO 25 25.65 7 730
Fe/Mn/PbO 25 23.80 7 738
Fe/Mn/PbO 25 26.30 7 741
Fe/Mn/PbO 75 75.08 8 733
Fe/Mn/PbO 75 86.46 8 742
Fe/Mn/PbO 75 79.50 8 746
Fe/Mn/PbO 75 71.40 8 749
Fe/Mn/PbO 75 68.77 8 751
Fe/Mn/PbO 225 215.68 9 719
Fe/Mn/PbO 225 237.34 9 721
Fe/Mn/PbO 225 199.45 9 729
Fe/Mn/PbO 225 240.58 9 744
Fe/Mn/PbO 225 263.25 9 745
IV 100 91.02 10 722
IV 100 129.79 10 724
IV 100 92.85 10 727
IV 100 107.56 10 734
IV 100 98.61 10 754
MEASUREMENT ENDPOINT
Blood
7.5
7.5
7.5
10.0
7.5
10.8
7.5
11.6
17.5
29.4
21.8
22.0
106.5 | b
45.5
50.9
10.0
12.2
7.5
11.5
12.7
28.2
42.6
44.1
33.3
40.5
82.6
94.7
78.4
67.6
73.9
28.8
12.2
27.1
8.4
18.1
33.7
25.4
32.2
23.9
53.0
83.4
115.5
123.9 j b
89.4
101.1
236.8
243.2
312.7
167.6
198.0
Femur
0.5
0.75
0.5
0.55
1.45
0.5
0.8
1.9
3.3
4
4.8
3.45
15.15 | b
6.1
5.05
1.2
1.8
3.55
0.5
1.35
3.25
3.05
5.05 | b
3.15
2.6
8.5
9.45
7.15
7.8
7.6
5.6
2
4.45
1.7
2
4.05
3.2
3.9
4.7
6
10.25
8.3
14.1 | b
11.7
11.8
52.5
42
43
56.5
42.1
Liver
10
10
10
10
10
27
30
45
134
113
92
81
681 I b
212
107
20
69
42
27
73
126
98
98
101
80
338
374
365
210 | b
295
65
42
52
35
58
85
117
88
177
242
456
258
566 | b
300
397
1540
2590
1520
1690
1480
Kidney
10
10
10
10
10
29
10
29
162
83
120
57
595 | b
143
104
10
39
27
35
46
138
89
67
124
74
286
300
287
232
216 | b
54
37
66
38
77
129
125
148
142
200
356
314
496 | b
399
436
1240
1260
1070
1060
1240
a a priori outlier determinations (none selected)
b Outside 95% Prediction Interval
-------
TABLE A-9 Best Curve Fit Parameters
Swtne Study Phase II Exp 7
BLOOD
PbAc Curve -
a
b
c
d
R2
Phase 1 Curve
a
b
c
d
R2
FeMnPbO Curve -
a
b
c
d
R2
Exp
6.2
BONE
PbAc Curve - Linear
a 1
b 0.0484
138.6
0.0045
0.258
Exp
*.2
138.6
0.0032
0.929
Exp
8.2
138.6
0.0039
0.9
Equations Used
EXP Y=a+c*(1-exp<-
-------
Swine Study Phase II Exp 7
TABLE A-10 Relative Bioavailability of Lead in Test Materials
Endpoint
Blood
Kidney
Liver
Bone
Test Material
Phase I
0.71
0.91
0.92
0.62
FeMnPbO
0.87
1.24
0.96
0.84
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
Phase I
0.71 0.82
0.71 0.76
0.74
FeMnPbO
0.87 1.01
0.87 0.94
0.90
Absolute Bioavailability
Plausible Range
Preferred Range
Point Estimate
Phase I
36% 41%
36% 38%
37%
FeMnPbO
43% 51 %
43% 47%
45%
-------
Swine Study Phase II Exp 7
TABLE A-11 INTRALABORATORY DUPLICATES
RPD = Relative Percent Difference
RPD = 10Q*[Orig-Dupl/({Orig+Dup)/2
* Non detects evaluated at 1/2 DL
Pig number
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
704
724
734
group material administered dosage
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
4
10
10
Phase 1
IV
IV
Phase 1
IV
IV
Phase 1
IV
IV
Phase 1
!V
IV
Phase 1
IV
IV
Phase 1
IV
IV
Phase I
IV
IV
Phase 1
IV
IV
Phase 1
IV
IV
Phase 1
IV
IV
Phase t
IV
IV
Phase 1
IV
IV
Phase 1
IV
IV
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
25
100
100
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 Duplicate Value*
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
0.5
0.5
0.5
0.5
0.5
0.5
0.5
12.2
8.2
0.5
17.3
11.3
0.5
13.7
9.4
0.5
16.8
9.3
0.5
18.6
14.7
0.5
20.3
13.8
0.5
16
11.7
0.5
16.9
12.9
1.65
52
52
54
1190
1060
10
2790
1690
Original Value*
0.5
0.5
0.5
0.5
0.5
0.5
0.5
11.8
7.7
0.5
15
9.2
0.5
13.5
9.6
0.5
17.7
11.1
0.5
16.7
13.3
1.5
21
12.5
0.5
16.5
12.1
0.5
16.7
13.1
1.2
42
56.5
10
1260
1060
20
2590
1690
Average
0.5
0.5
0.5
0.5
0.5
0,5
0.5
12
7.95
0.5
16.15
10.25
0.5
13.6
9.5
0.5
17.25
10.2
0.5
17.65
14
1
20.65
13.15
0.5
16.25
11.9
0.5
16.8
13
1.525
47
54.25
32
1225
1060
15
2690
1690
RPD
0%
0%
0%
0%
0%
0%
0%
-3%
-6%
0%
-14%
-20%
0%
-1%
2%
0%
5%
18%
0%
-11%
-10%
100%
3%
-10%
0%
3%
3%
0%
-1%
2%
-43%
-21%
8%
-138%
6%
0%
67%
-7%
0%
Avg RPD
2% BLOOD
-19% FEMUR
-44% KIDNEY
20% LIVER
-------
Swine Study Phase II Exp 7
TABLEA-12 CDC STANDARDS
Sample ID
7.1
7.1
7.1
7.1
7.1
7.2
7.2
7.2
7.2
7.2
7.2
7.2
7.2
7.3
7.3
7.3
7.3
7.3
7.3
7.3
Averages
Day Q
-4 <
0 <
1 <
3
g
-4
0
1
2
5
7
12
15
2
3
5
7
9
12
15
Measured
Low Std Med Std
1
1
1
5
1.1
4.9
4.3
4.3
4.6
4.6
3.8
3.7
3.7
1.82 4.2
Hiah Std
18.5
14.8
14.4
13
14.1
10.3
15.6
Nominal
Cone
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
14.4
-------
Swine Study Phase II Exp 7
TABLE A-13 INTERLABORATORY COMPARISON
Tag
Number
8-970158
8-970174
8-970208
8-970221
8-970249
8-970265
8-970313
8-970322
8-970370
8-970378
8-970401
8-970445
8-970452
8-970457
8-970511
8-970551
8-970577
8-970600
8-970618
8-970643
Pig
Number
709
737
724
708
729
738
751
740
739
752
718
753
711
730
741
752
743
747
702
716
Group
2
6
10
5
9
7
8
4
5
3
1
4
3
7
7
3
1
3
5
3
Material
Administered
PbAc
Phase I
IV
Phase I
Fe/Mn PbO
Fe/Mn PbO
Fe/Mn PbO
Phase I
Phase I
PbAc
control
Phase I
PbAc
Fe/Mn PbO
Fe/Mn PbO
PbAc
control
PbAc
Phase I
PbAc
Dosage
25
225
100
75
225
25
75
25
75
75
0
25
75
25
25
75
0
75
75
75
Qualifier
CDC
U
U
U
U
U
EPA
<
<
<
<
<
<
<
<
<
CDC
0.6
0.6
0.6
0.6
4.8
1
3.1
0.8
4.2
3.4
0.7
1.2
2.4
2.8
3.3
6.3
0.6
3.9
4.5
14.6
Result
EPA
1
1
1
1
3
1
1.7
1
3
2.3
1
1
1.9
2.2
2.2
5.8
1
2.4
3.7
12.9
Average
0.8
0.8
0.8
0.8
3.9
1
2.4
0.9
3.6
2.85
0.85
1.1
2.15
2.5
2.75
6.05
0.8
3.15
4.1
13.75
RPD
50
50
50
50
-46
0
-58
22
-33
-39
35
-18
-23
-24
-40
-8
50
-48
-20
-12
-------
8f CO I
*- *~ !
8!
ra
W
ฃ
Ittlttl
hp/Bn) gqd
-------
Swine Study Phase II Exp 7
FIGURE A-2 Phase I Groups by Day
Raw Data
-48i
-2
-ฎ 704
-H 712
736
- 740
-0 753
702
* --708
H- --728 |
a--739 I
O- --7561
-3K 7171
-&723!
-^&725 j
X 7321
-3K737
-------
Swine Study Phase II Exp 7
FIGURE A-3 FeMnPbO Groups by Day
Raw Data
a
1
Cfl
.o
0.
707
-ซ 713
-A 730
-A 738
-A 741
- ป---733
1 742
- & -746
-H---749
- - D- - -751
-X 719
-# 721
- 729
-B 744
745
-2
-------
Swine Study Phase II Exp 7
CD
.Q
Q.
FIGURE A-4 Group Mean PbB By Day
Raw Data
10 12 14 16
1 control
- 2 PbAc 25
- 3 PbAc 75
4 Phase I 25
5 Phase I 75
6 Phase I 225
7 Fe/Mn/PbO 25
8 Fe/Mn/PbO 75
9 Fe/Mn/PbO 225
10 IV 100
-------
Swine Study Phase II Exp 7
FIGURE A-5 COMPARISON OF DUPLICATE ANALYSES
Panel A
Blood Lead
Theoretical
y=1.00x+0.00
R2=1.00
Observed
= 0.97x
R2 = 0.99
8 10
Duplicate Value (ug/dL)
3000
2500 -I
|> 2000
a)
ซ 1500 --
"5
c
]i> 1000
6
500
500
Panel B
Tissue Lead
Theoretical
y=1.00x-K).00
R2=1.00
Observed
= 0.961x+14.7
R2 = 0.99
1000 1500
Duplicate Value (ug/L)
2000
2500
3000
Blind random duplicates submitted at a 5% rate to EPA laboratories to provide
a measure of analytical precision (reproducibility)
-------
Swine Study Phase II Exp 7
FIGURE A-6 CDCP CHECK SAMPLES
_l
5
D)
CO
^
Q.
_
PANEL A
-in
18
16
14
LowStd
B MedStd 12
ซ HighStd
LowStd 1Q.
- - - MedStd
High Std 8
6 -
mLD____ _________
4ซ
> -
ป 1 <
I ' I 0
5 -3 -1
ANALYSIS OF CDCP BLOOD LEAD CHECK SAMPLES
ซ 18.5
ซ 15.6
X lJ-ฐ * 14.4 ซ 141
ซ 13
ฎ 10.3
_ ..AJ) .,. ..
143343"*" "' "B
' B 3.8 B 3.7 B 3.7
> 1 ป 1 ป 1.1
1 3 5 7 9 11 13 15 1
Study Day
7
PANEL B INTERLABORATORY COMPARISON BETWEEN EPA AND CDCP
16
14
o>
00
_3
a.
2
HI
2
0
Theoretical
y-LOOx+O.OO
R2- 1.00
Observed
y - 0.74x + 0.62
R2 - 0.91
6 8 10
CDCP PbB Results (ug/dL)
12
14
16
-------
Swine Study Phase II Exp 7
ra
a
CD
o>
_o
DO
FIGURE A-7 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
Dose (ug Pb/kg-day)
Parameters
a
c
d
Value
6.2
138.6
0.0045
Std. Error
fixed value
fixed value
0.0007
95% Confidence Limits
-
0.0029
-
0.0061
AdjR2
0.258
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase I! Exp 7
FIGURE A-8 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Leadville Phase I Soil
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
100
05
O
o
CO
o>
T3
O
2
CQ
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
c
d
Value
6.2
138.6
0.0032
Std. Error
fixed value
fixed value
0.00019
95% Confidence Limits
0.0027
_
0.0036
AdjR
0.929
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 7
FIGURE A-9 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Leadville FeMnPbO Soil
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
150
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
c
d
Value
6.2
138.6
0.0039
Std. Error
fixed value
fixed value
0.00033
95% Confidence Limits
0.0032
~
0.0046
AdjR
0.900
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 7
FIGURE A-10 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
Dose (ug Pb/kg-day)
Parameters
a
b
Value
1.0
0.0484
Std. Error
fixed value
0.007
95% Confidence Limits
0.033
0.064
I Adj R2 0.632
Generated using Table Curve 20 v. 3.0. Outliers represented by"+".
-------
Swine Study Phase I! Exp 7
FIGURE A-11 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
^
CD
tf>
CO
-5*
-D
CL
O)
73
CO
o
00
10
9-
8-
7-
6-
5-
4-
3-
2-
1-
0
MATERIAL: Leadville Phase I Soil
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
1.0
0.0298
Std. Error
fixed value
0.0014
95% Confidence Limits
0.027
0.033
AdjR
0.932
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 7
FIGURE A-12 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: Leadville FeMnPbO Soil
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
0)
.
CO
CO
a.
CD
T3
CO
o
CO
100 200
Dose (ug Pb/kg-day)
300
Parameters) Value | Std. Error
a
b
1.0
0.0407
fixed value
0.0027
95% Confidence Limits
0.035
0.046
AdjR2 0.858
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 7
FIGURE A-13 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
Dose (ug Pb/kg-day)
Parameters] Value
a
b
15.3
1.482
Std. Error
fixed value
0.267
95% Confidence Limits
0.904
2.06
AdjR2
0.465
Generated using Table Curve 2D v. 3.0. Outliers represented by "+".
-------
Swine Study Phase II Exp 7
FIGURE A-14 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
400
_ 350-
- 300-
I5 250 H
!3
D.
S> 200 H
CO
0)
0)
150-
100-
50-
0
MATERIAL: Leadville Phase I Soil
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
15.3
1.358
Std. Error
fixed value
0.060
95% Confidence Limits
1.23
1.48
AdjR2
0.942
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 7
FIGURE A-15 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
I
O)
O)
3.
o
CD
O>
.1
600
500-
400-
MATERIAL Leadville FeMnPbO Soil
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters | Value
a
b
15.3
1.421
Std. Error
fixed value
0.107
95% Confidence Limits
1.195
1.65
| AdjR2 0.833 I
Generated using Table Curve 2D v. 3.0. Outliers represented by"+",
-------
Swine Study Phase II Exp 7
FIGURE A-16 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
600-
1 500'
Q_
O>
400-
300-
20
40
Dose (ug Pb/kg-day)
60
Parameters | Value | Std. Error
a
b
15.1
1.233
fixed value
0.263
95% Confidence Limits
~
0.664
1.802
AdjFT
0.359
Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 7
FIGURE A-17 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
I
CO
TJ
CD
-------
Swine Study Phase II Exp 7
FIGURE A-18 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
500
05
-a
O3
.3
MATERIAL: Leadville FeMnPbO Soil
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
15.1
1.535
Std. Error | 95% Confidence Limits
fixed value
0.053
1.42
_
1.65
Adj R
0.961
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
SECTION B
STUDY 8
AV Slag
-------
Sludy Phai* H Eaji B
TABLE B-1 BODY WEIGHTS AND ADMINISTERED DOSES, BY DAY
Body weights were measured on days-1,2.5.8, 11,14, Weights for othtf days are estimated, basedonlnearinterpolalioilbetweenfneasuredvaliies.
Group ID*
5 809
5 830
5 841
5 848
5 855
6 817
6 818
6 819
6 838
6 846
7 804
7 840
7 842
7 844
7 849
6 802
8 826
B 826
a 831
8 851
9 806
9 814
9 823
9 847
9 854
10 811
10 822
10 824
10 837
10 856
Oay-1
BW ugPb
jfcfj) per day
8.54 D
8.98 0
8.24 0
1014 0
9.36 0
8.72 D
9.92 0
7.64 0
9.26 0
7.82 0
8.24 D
10.72 0
8.5 0
8.58 0
7.78 0
7.94 0
9.26 0
10.64 0
7.58 0
826 a
8,8 0
9.6 0
8.54 0
9.24 0
9.12 D
8,42 0
9.24 0
7.68 0
8.72 0
7.36 0
DayO
BW ygPb
(kg) per day
8.B 0
8.S 0
8.4 0
106 0
93 0
9.2 242
10.3 242
79 242
94 242
8,t 242
8.4 732
11.1 732
8.8 732
9.0 732
8.2 732
8.1 243
9.4 243
10.6 243
7.4 243
83 243
9.2 755
9.9 755
8.8 755
9.6 755
95 755
8.B 208S
9.5 2089
8.2 2089
87 2089
7.6 2089
Day1
BW ygPb
(kg} per day
9,1 0
8.6 0
8.6 0
11.1 0
10.2 0
9.6 242
10.7 242
8,1 242
9.6 242
8.3 242
8.5 732
11.4 732
9.1 732
9.4 732
8.6 732
8.2 243
9.5 243
10.5 243
7.2 243
83 243
9.5 755
10.3 755
9.1 755
10.0 755
99 755
9.1 2089
9.7 2089
8.6 2088
86 2089
79 2089
Day2
BW ugPb
(kg) perday
9.32 0
8.46 0
8.78 0
11.54 0
106 0
10.04 242
11.06 242
3,23 242
9.7 242
854 242
8.6 732
11.72 732
9.34 732
9.76 732
6.96 731
8.34 243
9.56 243
10.4
7 243
6.36 243
9.88 755
10.64 755
9.36 755
10.44 755
10.34 755
9.48 2089
10 2089
9.12 2089
854 2089
8.12 2089
Day 3
BW ugPb
(kg) per day
9.8 0
88 0
9,3 0
11.S 0
10.5 0
10.5 263
11.3 263
8.6 263
10.1 263
9.0 263
8.8 801
12.0 801
9.8 801
10.0 801
94 801
8.8 243
10.2 243
w*>mm
7,3 243
8.9 243
10.2 835
11.1 835
9.8 835
10.8 835
10.7 635
9.9 2262
10.4 2262
9.5 2262
86 2262
8.5 2262
Day4
BW ugPb
(kg) per day
10.2 0
9.2 0
9.9 0
12.4 0
10.5 0
10.9 263
11.6 263
8.8 263
10.5 263
9.4 263
9.1 801
12.3 801
10.3 801
10.3 801
9.9 801
9.3 243
10.7 243
io.as;!ซ!;
7.6 243
9.4 243
105 835
11.5 835
10.2 835
11.1 835
11.0 835
10.3 22S2
10.8 2262
9.9 2262
8.6 2262
8.6 2262
Days
BW ugPt
(kg) per day
10.7 0
9.62 0
10.44 0
12.76 0
10.44 0
11.4 263
11.88 263
3.12 2S3
10.96 263
9.8 263
9.34 801
12.6 801
10.72 801
10.54 801
10.36 801
982 243
11.34 243
11.02 243
7.86 243
9.92 243
10.84 835
11.92 835
10.58 835
11.42 835
11.28 635
10.68 2262
11.16 2262
10.36 2262
864 2262
912 22S2
Day 6
BW og Pi!
(kg) per day
14.9 0
12.6 0
14.4 0
16,8 0
15.2 0
15.3 348
13-7 348
13.3 348
14.6 348
13.9 34B
12.6 1073
164 1073
15.9 1073
14.6 1073
14.7 1073
138 332
148 332
15 332
11.8 332
13 332
14.6 1118
16.7 1118
14.6 1118
15.2 1118
16.2 1118
14.5 2935
15.8 2935
14.3 2935
11,2 2935
13.3 2935
Day 15
BW ugPb
(kg) per day
15.4 0
13.0 0
15.1 0
17.3 0
15.7 0
15.6 0
142 0
13.9 0
14.8 0
144 0
130 0
16.9 0
16.6 0
15.0 0
15.2 0
143 0
15.3 0
15.5 0
12.3 0
13.4 0
15.1 0
17.2 0
14.9 0
15.8 0
16.9 0
15.3 0
16.5 0
14,9 0
11.7 0
13.7 0
S:?:ฃฃx Shaded boxes shew days in which Bdniinstered doses were ingested iafe
-------
TABLE B-2
Body Weight Adjusted Doses
(Dose for Oay/BW for Day)
Swine Stufy Phase II Bep 8
Group
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
a
8
8
8
8
9
9
9
9
9
10
10
10
10
10
ID*
809
830
841
848
855
817
818
819
838
346
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
DayO
0.0
0.0
0.0
0.0
0.0
26.4
23.5
30.8
257
30.0
87.6
663
83,4
81.6
89.6
30.1
28.0
23.0
330
29.3
82.4
759
85.6
78.3
79.2
2381
220.0
256.0
241.2
274.4
Day)
0.0
0.0
0.0
0.0
0.0
25.2
22.6
30.0
253
291
86.4
64.3
80.8
78.2
855
29.7
25.7
232
33.8
292
793
733
83.0
75.1
760
228.9
214.3
241.8
242.9
265.5
Day 2
00
00
00
00
0.0
24.1
21.9
29.2
24.9
28.3
85.2
62.5
78.4
75.0
81.7
29.2
25.5
23.4
34.8
29.1
76.4
70.9
80.6
72.3
73.0
220,3
2089
229.0
2446
257.3
Day 3
0.0
0.0
0.0
0.0
0.0
25.1
232
30.7
260
29,4
90.5
66.7
81.7
79.9
84.9
27.5
240
229
334
27.4
81.9
75.4
85,5
77.5
78,4
2289
2178
237.2
2638
267,6
Day 4
0.0
0.0
00
00
00
24.0
22.7
29.8
25.0
28.0
88.1
65.1
78.0
77.9
80.9
26.1
22.6
22.5
32.1
25.9
79.4
72.6
82.1
753
76.1
220.0
209.9
227.4
2628
257.4
Days
00
0.0
00
0.0
0.0
23.1
22.1
28.8
24.0
26.8
85,7
63.5
74.7
76.0
77.3
24.8
21.5
22.1
31.0
24.5
77.0
70.0
78.9
73.1
74.0
211.8
202.7
218.3
261.8
248.0
Day 6
00
0.0
0,0
00
0.0
24.3
23.9
30.2
257
28.4
90.6
686
78.5
80.0
81.0
27.5
23.9
24.1
332
27.0
81.4
73. S
82.4
77.6
77,3
226.8
211.4
233.6
2825
260.2
Day?
0.0
0.0
0.0
00
0.0
23.3
234
287
250
27.2
87.3
67.5
754
77,0
776
27.0
23,5
233
316
264
786
71,2
787
752
73.8
2221
202.1
228.7
2789
250.0
DayS
0.0
0.0
0.0
0.0
0.0
22.3
22.9
27.4
24.3
26.2
84.3
664
725
74.2
74.4
26.6
23.2
226
30.1
25.8
75.9
68.6
75.3
72.9
70.5
2177
193,5
224.0
275.4
240.6
DayS
00
0.0
0.0
00
0,0
23.9
257
29.5
25.5
27.8
89.6
702
764
784
788
26.9
23.9
234
31.0
26.8
820
73.3
80.7
79.8
763
2299
204.1
231.7
290.3
246.1
Day 10
0.0
0.0
0.0
00
0.0
23.2
26.0
28.7
243
26.8
86.7
676
73.3
75.4
75.9
25.4
22,9
226
29.7
25.9
79.5
70.3
77.6
78.3
74.1
224.6
199.1
221.9
283.1
233.5
Day 11
0.0
0.0
00
00
0.0
22.6
26.2
27.9
231
258
84.0
651
70S
72,6
733
24.1
220
21.9
28.5
25.0
77.2
675
74.8
76.9
71.9
2196
194.4
213.0
2763
222.2
Day 12
0.0
0.0
0.0
0.0
0.0
238
27.2
28.7
24.6
26.8
90.4
696
74.3
78.1
78.4
26.0
23.9
23.7
30.6
27.2
81.6
71.4
80.0
80.3
75.2 -
2286
2032
2234
2881
2355
Day 13
0.0
0.0
0.0
0.0
0.0
23.2
26.3
27.3
24.2
25.9
877
676
70.7
75.7
75.6
25.0
23.1
22.9
29.3
26.3
790
69.1
78.2
76,8
72.0
2138
194.1
2139
274.5
2279
Day 14
0.0
0.0
0.0
0.0
0.0
22.7
25.4
261
238
25.0
851
65.4
67.5
735
730
24.1
22.4
22.1
28.1
25.5
76.6
669
76.6
73.5
69.0
2024
1858
205.2
262,0
220.7
Avg Dose
00
00
0.0
00
0,0
23.8
24.2
28.9
24.8
27.4
87.3
65.4
75.7
78.8
792
26.7
23.6
229
31.3
268
79.2
71.4
80.0
78.2
744
222.1
204.1
227.0
268.6
247.1
Target Dose
ป
9
$
o
0
26
2S
29
25
25
' 75
Ts
75
W
25 "
25
25
25
ฃ5
TS
75
?5
ts
225
225
22S
225
225
V, Tarflet
95
97
118
99
110
116
89
101
103
106
107
94
92
125
107
108
95
107
102
99
99
91
101
119
110
Avg%
103
103
105
102
104
-------
TABLE B - 3 RAW AND ADJUSTED BLOOD LEAD DATA
S*r* Study Ptuu II E*p 8
pig number
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817 ,
818
819
838
846
804
840
B42
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
ample
8-980121
8-980170
8-980171
8-980169
8-980120
8-980154
8-980162
8-980157
8-980122
8-980124
8-980156
8-980167
8-980129
8-980158
8-980138
8-980150
8-980139
8-980147
8-980131
8-980166
8-980132
8-980152
8-980143
8-980153
8-980148
8-980130
8-980133
8-980136
8-980141
8-9B0159
8-980213
8-980210
8-980197
8-980200
8-980209
8-980192
8-980176
8-980222
8-980220
8-980204
8-980198
8-980185
8-980187
8-980212
8-980177
8-980223
8-980203
8-980225
8-980179
8-980199
8-980202
8-980183
8-980194
8-980193
8-980211
8-980219
8-980221
8-980174
8-980178
8-980180
8-980227
8-980276
8-980270
8-980272
8-980260
8-980239
8-980274
8-980258
8-980254
8-980244
8-980252
8-980251
8-980234
8-980256
8-980267
8-980240
8-980266
8-980261
8-980263
8-980257
8-980237
8-980226
8-980233
8-980241
8-980271
8-980255
8-980273
8-980245
group
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
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
8
a
8
8
9
9
9
9
9
10
10
10
10
10
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
material administered
Control
Control
Control
Control
Cortrol
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
dosage qu
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
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
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 <
Lab result
ifier (ug/L)
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
1.7
1.3
1.8
1.1
1
1.2
1
1
1
1
1.5
1.1
1
1
1
1
1
day
-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
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
source file
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951 101
T951 101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
MATRIX
BLOOD
SLQOD
BL000
BLOOD
8LQOD
BLOOD
SLQOD
BLOOD
BLOOD
BLOOD
BIOQ'D
BLOOD
BLOOD
flLODD
BLOOD
atQOD
BLOOD
BLOOD
fiiOOD
BLOOD
8LQOD
BLOOD
SLQOD
BLOOD
BLOOD
BLOOD
' SIQQD
SLQOD
BLOOD
BLOOD
SLQOD
BLOOD
BLOOD
BLOOD
miOQQ
BLOOD
BLOOD
flLODD
BLOOD
61.000
BLODD
BLOOD
BLOCK)
BLOOD
BLOOD
flLODD
BLOOD
BLOOD
flLODD
BLOOD
SiOOD
' BLOOD
8LOOD
BLOOD
BLQQO
BLOOD
BLOOD
BLOOD
BLQ00
BLOOD
BLOOD
BLOOD
BLOOD
flUSQD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLODD
SUSOO
fltOOQ
BLOOD
BLOOD
BLOOD
BLOOD
8LQOD
BLOOD
StQOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
Adjusted Value* Notes
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
Cloned
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
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
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.7
1.3
1.8
1.1
0.5
1.2
0.5
0.5
0.5
0.5
1.5
1.1
0.5
0.5
0.5
0.5
0.5
-------
ฃ*ป Study PhM. II Exp 6
material administered dosage
qualifier (uo,/L)
day
eourca file
Adjusted Value'
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
8-980236
8-980262
8-980310
8-980289
8-980330
S-9B0281
8-980323
8-980316
8-980299
8-980322
8-980280
8-980331
8-980320
5-980Z90
8-980297
8-980294
8-980313
8-980312
8-980325
8-980317
8-980305
8-980285
8-980321
8-980315
8-980296
8-980328
8-980286
8-980318
8-980319
8-980293
8-980284
8-980283
8-980342
8-980355
8-980357
8-980333
8-980361
8-980370
8-980352
8-980382
8-980337
8-980356
8-980372
8-980345
8-980373
8-980383
8-980359
8-980358
8-980349
8-980380
8-980350
8-980367
8-980354
8-980379
8-980343
8-980360
8-980364
8-980340
8-980353
8-980365
8-980377
8-980336
8-980434
8-980401
8-980393
8-980405
8-980406
8-980389
8-980416
8-980394
8-980422
8-980427
8-980410
8-980428
8-980413
8-980425
8-980433
8-980390
8-980407
8-980385
8-980404
8-980402
8-980426
8-980391
8-980399
8-980400
8-980419
8-980431
8-980429
8-980397
8-980417
10
10
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
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
a
a
8
8
9
9
9
9
9
10
10
10
10
10
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
a
a
a
8
8
9
9
9
9
9
10
10
10
10
AVSlag
AVStag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AV Slag
AV Slag
AVSlag
AVSlag
AVSlag
AV Slag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Control
Conlrol
Conlrol
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AV Slag
AV Slag
AV Slag
AVSlag
AVSlag
AV Slag
AVSlag
AV Slag
AV Slag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Conlrol
Control
Control
Conlrol
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
225 <
225 <
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 <
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
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
1
1
1
1
1
1
1.8
1
1
1
1.9
1
1.7
1.5
18
1
1
1
1
1
1
1.4
1
1
1
1
1
1
2.9
1
1
1.7
1
1
2.4
1.7
1.9
1
1
1
1
1
1
1
1.3
1.5
1.5
1
2.8
2
1.6
1.7
1.7
1
1
1
1
1
1.7
1
3
1.3
1
2.8
3.2
2.7
2.1
1
1
1.3
1
1
1
1
1.6
1.2
2.5
2.3
2.5
1.2
2.6
4.5
1
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
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
T951 101
T951101
T951101
T951101
T951 108
T951101
T951 101
T951101
T951101
T951101
T951101
T951 108
T951101
T951101
T951101
T951101
T951 101
T951101
T951 101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951101
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
7951108
T951108
T951108
T951108
T951 108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951108
1951108
T951108
T951108
1951108
1951108
7951108
T951108
1951108
1951108
T951108
T951108
T951108
T951108
T951108
T95110B
T951108
T951 108
T951108
T95110B
T951108
T951108
T951108
T951108
T951108
BLOOD
SLOW
BLOOD
BLOOD
SLOOD
81000
BLODO
SLOOD
BLODD
BLOOO
BLOOD
BLOOD
BLOOD
81000
BLOOD
SLQOD
BLODD
BLOOD
BLOOD
BLODD
8LOOD
BLOOD
BLOOD
BLOOD
BLODD
BLOOD
8LOOD
BLODD
BLOOD
8LOOD
BLOOO
BLOOD
BLOOD
BLOOO
BLOOO
BLODD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLODD
BLOOD
BiOOD
BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLODD
8LQOD
91000 . .
. BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLODD
BLOOD
8L00D
BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLODD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
BLODD
SLOOD
filOOO
BLOOD
SLOOD
BLODD
BLOOD
8LOOD
0.5
0.5
0.5
0.5
0.5
0.5
1.8
0.5
0.5
0.5
1.9
0.5
1.7
1.5
1.8
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
1
1
1.4
0.5
0.6
0.5
0.5
0.5
0.5
2.9
0.5
0.5
1.7
0.5
0.5
2.4
1.7
1.9
1
0.5
0.5
0.5
0.5
0.5
0.5
1.3
1.5
1.5
1
2.8
2
1.6
1.7
1.7
0.5
0.5
0.5
0.5
0.5
1.7
1
3
1.3
0.5
2.8
3.2
2.7
2.1
1
0.5
1.3
0.5
0.5
0.5
0.5
1.6
1.2
2.5
2.3
2.5
1.2
2.6
4.5
-------
pig number sample
material administered dosage
qualifier (ug/L)
day
source file
BEATRIX
Adjusted Value*
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
8-980435
8-980447
8-980443
8-980488
8-980448
8-980472
8-980489
8-980449
8-980469
8-980486
8-980483
8-980452
8-980473
8-980480
8-980477
8-980446
8-980442
8-980471
8-980475
8-980465
8-980476
8-980468
8-980450
8-980458
8-980438
8-980459
8-980474
8-980454
8-980462
8-980485
8-980456
8-980495
8-980541
8-980534
8-980492
8-980507
8-980512
8-980543
8-980535
8-980539
8-980536
8-980497
8-980513
8-980538
8-980518
8-980514
8-980494
8-980526
8-980523
8-980520
8-980542
8-980491
8-980516
8-980498
8-980519
8-980496
8-980506
8-980530
8-980533
8-980521
8-980531
8-980560
8-980546
8-980552
8-980565
8-980556
8-980547
8-980578
8-980569
8-980596
8-980563
8-980570
8-980594
8-980581
8-980577
8-980574
8-980557
8-980595
8-980589
8-980551
8-980585
8-980592
8-980593
8-980573
8-980558
8-980579
8-980591
8-980584
8-980582
8-980580
8-980566
10
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
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
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
AVStag
Control
Control
Control
Control
Control
PbAc
PbAc
PtoAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AV Slag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
225
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
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
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
1.5
1
1
1
1
1
2.6
1
1
1.8
1.7
3.5
4.1
3.6
2.6
1
1.1
1
1
1
1
1
1.7
1
2
1.7
2.2
2.1
1.3
3.7
1.9
1
1
1
1
1
1.8
1
1.9
1.7
1.9
3.5
5.4
2.5
3
1
1.1
1
1
1
1
1
1.6
2.8
3
2
2.2
2
2.8
3
1.8
1
1
1
1
1
2.5
1.8
1.3
2.5
1.6
4.3
5.9
3.3
2.9
2.5
1
1.1
1
1
1.7
1
2
2.6
3.2
26
2.1
3.3
4.3
2.8
1.9
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
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
12
12
12
12
12
12
12
12
12
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951 108
T951 108
T951108
T951108
T951108
T951108
T951108
T951 108
T951108
T951 108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951 108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
BLOOD
BLOOD
BLOOD
BLOOD
8LQQ0
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOP
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
8LQOD
BLOOD
BLOOD
BLOOD
BLOOD
BtOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLODQ
BLOOD
81.000
BLOOD
SLOOD
BIOOO
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
BLOOP
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
.BLOOD ..
BLOOD
BLOOD
BLOOD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLQQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
1.5
0.5
0.5
0.5
0.5
0.5
2.6
0.5
1
1.8
1.7
3.5
4.1
3.6
2.6
0.5
1.1
0.5
0.5
0.5
0.5
0.5
1.7
1
2
1.7
2.2
2.1
1.3
3.7
1.9
0.5
0.5
0.5
0.5
0.5
1.8
0.5
1.9
1.7
1.9
3.5
5.4
2.5
3
0.5
1.1
0.5
0.5
0.5
0.5
1
1.6
2.8
3
2
2.2
2
2.8
3
1.8
0.5
0.5
0.5
0.5
0.5
2.5
1.8
1.3
2.5
1.6
4.3
5.9
3.3
2.9
2.5
0.5
1.1
0.5
0.5
1.7
0.5
2
2.6
3.2
2.6
2.1
3.3
4.3
2.8
1.9
-------
Sซn Study Phnซ II Eip 6
pig number sample group
material administered dosage
qualifier (ug/L)
day
MATRIX
Adjusted Value'
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
8-980635
8-980606
8-980605
8-980624
8-980627
8-980600
8-980601
8-980613
8-980646
8-980642
8-980648
8-980622
8-980637
8-98061 1
8-980597
8-980631
8-980619
8-980639
8-980626
8-980616
8-980629
8-980599
8-980621
8-980630
8-980615
8-980604
8-980617
8-980641
8-980608
8-980607
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
a
8
8
8
8
9
9
9
9
9
10
10
10
10
10
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc "
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AV Slag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
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
1
1
34
3.7
2.1
5.8
7,6
4.6
4.1
3.1
1.3
1.6
1
1
1.2
1
3
2.3
3.9
2.2
2.5
3.7
4.4
2.7
2.8
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
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T95110S
T951108
T951108
T951108
T951108
T951108
T95110S
T951108
T951108
T951108
T951108
T951108
T951108
T951108
T95110B
T951108
T951108
T951108
T95110B
BLOOD
SM300
8LOOO
BLQOd
8LOOD
810QO
SLOOD
StOOD
BLOOD
SLQOO
BLOOD
SLOOO
8LOOO
81,000
etooo
SLOQD
BLOOD
euooo
BLOOD
BLOOD
8LOOD
etooo
8LOOO
BLOOD
BLO0D
BLOOD
&.OOO
BLOOD
BLOOD
. 8LOOO .
0.5
0.5
0.5
0.5
0.5
3.4
0.5
1
3.7
2.1
5.8
7.6
4.6
4.1
3.1
1.3
1.6
0.5
0.5
1.2
0.5
3
2.3
3.9
2.2
2.5
3.7
4.4
2.7
2.8
Non-detects evaluated using 1/2 the quantitation limit; laboratory results (ug/L) converted to concentration in blood (ug/dL) by dividing by dilution factor of 1 dlTL
-------
Swฅw Study PtuM II Ejp 6
TABLE B-4 BLOOD LEAD OUTLIERS
Flagged Data Points
| [Outliers (none selected)
test target
material dosage
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
Actual
Dose*
0.00
0.00
0.00
0.00
0.00
23.81
24.20
28.92
24.77
27.43
87.28
6643
75.75
76.90
79.20
group
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
pig*
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
-4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
o.s
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
O.S
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.7
1.3
1.8
1.1
2
0.5
0.5
0.5
0.5
0.5
1.8
0.5
0.5
0.5
1.9
0.5
1.7
1.5
1.8
0.5
BLOOD
3
0.5
0.5
0.5
0.5
0.5
2.9
0.5
0.5
1.7
0.5
0.5
2.4
1.7
1.9
1
LEAD (ug/dL) BY DAY
5
0.5
0.5
0.5
0.5
0.5
1.7
1
3
1.3
0.5
2.8
3.2
2.7
2.1
1
7
0.5
0.5
0.5
0.5
0.5
2.6
0.5
1
1.8
1.7
3.5
4.1
3.6
2.6
9A
9
0.5
0.5
0.5
0.5
0.5
1.8
0.5
1.9
1.7
1.9
3.5
54
2.5
3
<3*
12
0.5
0.5
0.5
0.5
0.5
2.5
1.8
1.3
2.5
1.6
4.3
5$
3.3
2.9
2.5
15
0.5
0.5
0.5
0.5
0.5
3.4
0.5
1
3.7
2.1
5.8
7$
4.6
4.1
3.1
Average Time and Weight-Adjusted Dose for Each Pig
-------
Swine Study Phase II Exp 8
TABLE B-5 RATIONALE FOR PbB OUTLIER DECISIONS
NO PbB OUTLIERS SELECTED FOR THIS EXPERIMENT
-------
Swine Study Phase II Exp 8
TABLE B-6 Area Under Curve Determinations
Calculated using interpolated values for missing or excluded data
AUC (ug/dL-days) For Time Span Shown
Pifl#
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
0-1
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
0.50
1.10
0.90
1.15
0.80
0.50
0.85
0.50
0.50
0.50
0.50
1.00
0.80
0.50
0.50
0.5.0
0.50
0.50
0.50
0.50
1-2
0.50
0.50
0.50
0.50
0.50
1.15
0.50
0.50
0.50
1.20
0.50
1.70
1.40
1.80
0.80
0.50
0.85
0.50
0.50
0.50
0.50
1.00
0.80
0.50
0.75
0.50
0.75
0.75
0.95
0.50
2-3
0.50
0.50
0.50
0.50
0.50
2.35
0.50
0.50
1.10
1.20
0.50
2.05
1.60
1.85
0.75
0.50
0.50
0.50
0.50
0.50
0.50
0.90
1.00
1.00
1.00
1.65
1.50
1.30
1.55
1.10
3-5
1.00
1.00
1.00
1.00
1.00
4.60
1.50
3.50
3.00
1.00
3.30
5.60
4.40
4.00
2.00
1.00
1.80
1.00
1.00
1.00
1.00
2.90
2.70
4.00
3.30
5.30
3.20
4.20
6.20
3.20
5-7
1.00
1.00
1.00
1.00
1.00
4.30
1.50
4.00
3.10
2.20
6.30
7.30
6.30
4.70
1.50
1.60
1.80
1.00
1.00
1.00
1.00
3.30
2.20
4.50
4.00
4.70
3.30
3.90
8.20
3.40
7-9
1.00
1.00
1.00
1.00
1.00
4.40
1.00
2.90
3.50
3.60
7.00
9.50
6.10
5.60
1.00
2.20
1.00
1.00
1.00
1.00
1.50
3.30
3.80
5.00
3.70
4.40
4.10
4.10
6.70
3.70
9-12
1.50
1.50
1.50
1.50
1.50
6.45
3.45
4.80
6.30
5.25
11.70
16.95
8.70
8.85
4.50
2.40
2.40
1.50
1.50
3.30
2.25
5.40
8.10
9.30
6.90
6.45
7.95
10.65
8.70
5.55
12-15
1.50
1.50
1.50
1.50
1.50
8.85
3.45
3.45
9.30
5.55
15.15
20.25
11.85
10.50
8.40
2.70
4.05
1.50
1.50
4.35
1.50
7.50
7.35
10.65
7.20
6.90
10.50
13.05
8.25
7.05
AUC Total
(ug/dL-days)
7.50
7.50
7.50
7.50
7.50
32.60
12.40
20.15
27.30
20.50
44.95
64.45
41.25
38.45
19.75
11.40
13.25
7.50
7.50
12.15
8.75
25.30
26.75
35.45
27.35
30.40
31.80
38.45
41.05
25.00
-------
Smn* Study PTuปs I! Exf> 8
TABLE B - 7 TISSUE LEAD DATA
pig numb
809
630
641
848
855
817
818
819
838
846
804
840
842
844
849
802
826
628
831
851
806
814
823
847
654
611
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
802
826
828
831
851
806
814
823
847
854
811
822
824
837
856
ter sarnpls
8-980814
8-980827
8-980799
8-980812
8-980622
8-980785
8-960786
8-980809
8-980818
8-980787
8-980811
8-960607
8-980824
8-980791
8-960816
8-980792
8-980826
8-980803
8-980815
8-980783
8-980830
8-980790
8-980831
8-960601
8-980820
8-980829
8-980793
8-980798
8-980817
8-980784
8-980744
8-980770
8-980762
8-980750
8-980756
8-980765
8-960768
8-980777
8-980743
8-960742
8-980751
8-980748
8-980764
8-980734
8-980749
8-980740
8-980746
8-980758
8-980797
8-980772
8-980786
8-980757
8-980736
8-980780
8-980776
8-980774
8-960773
8-960752
8-980754
8-980760
8-980696
8-980690
8-980700
8-980714
8-980894
8-980685
8-980686
8-980709
8-980728
8-980721
8-980707
8-980693
8-980723
8-980683
8-980898
8-980718
8-980699
8-980728
8-980729
8-980725
8-980689
8-980692
8-980680
8-980713
8-980708
8-980724
8-980706
8-980727
8-980720
8-980681
group
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
8
6
6
Q
8
9
9
9
9
9
10
10
10
10
10
5
5
5
5
5
6
8
6
6
6
7
7
7
7
7
8
8
8
a
8
9
9
9
9
9
10
10
10
10
10
5
5
5
5
5
6
8
6
6
6
7
7
7
7
7
8
8
8
8
8
9
9
9
9
9
10
JO
10
10
10
material administered dosag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AV Slag
AV Slag
AVSlag
AVSlag
AVSlag
AVSlag
AV Slag
AV Slag
AVSlag
AVSlag
AVSlag
AV Slag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AV Slag
AVSlag
AV Slag
AVSlag
AV Slag
AV Slag
AV Slag
AVSlag
AVSlag
AV Slag
AV Slag
AVSlag
AV Slag
AVSlag
AV Slag
Control
Control
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
AVSlag
Qualifier
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
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
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
Lab result
(ug/L)
3
2
2
2
2
5.1
4.4
2.8
7.4
6.5
9
11.1
13.2
13
6.4
2.4
81
2.9
4.1
4.1
2.7
4.9
4.9
5.4
4
5
9.8
5
8.7
5
2.1
2
4
2.5
9.1
10.4
3.2
3.5
10
9.6
22
21.4
34.9
23
8.4
28
4.9
11.6
5.6
2
1.9
9.4
5.7
6.3
4.8
5.8
13
8.2
7.3
7.6
2
2
2
2
8.5
16.2
5.2
2
5.8
2.7
23.9
21.6
23.8
15.3
12.4
8.7
2.8
2
7
2
2.4
7.5
5
9.5
2.7
7.7
15
8.1
8.2
2.9
day
15
15
15
IS
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
IS
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
source file
TB60131F
T980131F
T980131F
T980131F
T960131F
T960131F
T960131F
T960131F
T960131F
T980131F
T980131F
T980131F
T980131F
T980131F
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
T980120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120K
T980120K
T960120K
T980120K
T960120K
T960120K
T960120K
T960120K
T960120K
T960120L
T960120L
T960120L
T960120L
T960120L
T980120L
TS80120L
T960120L
T960120L
T960120L
T960120L
T980120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T960120L
T980120L
T980120L
T960120L
T960120L
T960120L
T860120L
T960120L
T960120L
T960120L
T980120L
T960120L
MATRIX
FEMUR
FQiWR
FEMUfl
PENUfl
fEtJUR
FEMUR
FEMUfl
FEWUft
FEMUR
FEWUS
FBJUfl
FEMUR
FEMUR
FWWR
F6MUR
FEMUR
FEMUR
FWUB
F8ซJซ
FEMUR
FEMUR
FBilUR
FEMUS
PEMUS
FEMUR
FBHUR
FEMUfl
FEMIW
FEMUR
FEMUR
KIDNEY
KIBNer
KI6N6V
KIDNEY
KIDNEY
KIONEY
KltOTEY
KIDNEY
KIDNEY
KIOHeY
KIONSY
KIDNEY
KIDNEY
KioNer
KIDN6Y
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
W3NSY
KIDNEY
KIDNEY
KIQNEY
KloneY
KIDNEY
KIDNEY
. , isioNeY
UVSR
OVER
UV6R
uvsr;
UVE*
LIVER
LIVSR
MVER
L1VER
UVER
LIV66
UVEB
1IVฃR
UVSR
LIV6R
WVEB
t1V6ft
UVER
LIVER
uvert
UVER
ซVER
LIVER
MVER
UVfiR
tlVER
UV6R
UVER
11VBI*
1JWSR
Adjusted Value* Notes
1.5
0.5
0.5
0.5
0.5
2.55
2.2
1.4
3.7
4.25
4.5
5.55
9.6
6.5
4.2
1.2
4.05
1.45
2.05
2.05
1.35
2.45
2.45
2.7
2
2.5
4.9
2.5
4.35
2.5
21
10
40
25
91
104
32
35
100
98
220
214
349
230
64
260
49
116
se
10
19
94
57
93
48
56
130
82
73
76
10
10
10
10
85
162
52
10
58
27
239
216
236
153
124
67
28
10
70
10
24
75
50
95
27
77
150
81
82
29
Non-detects evaluated using 1/2 the quantitation frrit. Laboratory results (ug/L) converted to tissue concentrations by dividing by sample dilution factor* of
0.1 kg/L {Nver, kidney) or 2 g/L (ashed bone). Final units an ug Pb/kfl wet weight (liver, kidney) or ug Pb/g ashed bone (femur)
-------
Swine Study Phase II Exp 8
TABLE B-8 SUMMARY OF ENDPOINT OUTLIERS
J Selected Outliers
test target Actual
material dosage Dose* group pig#
Control 0 0.00 5 809
Control 0 0.00 5 830
Control 0 0.00 5 841
Control 0 0.00 5 848
Control 0 0.00 5 855
PbAc 25 23.81 6 817
PbAc 25 24.20 6 818
PbAc 25 28.92 6 819
PbAc 25 24.77 6 838
PbAc 25 27.43 6 846
PbAc 75 87.28 7 804
PbAc 75 66.43 7 840
PbAc 75 75.75 7 842
PbAc 75 76.90 7 844
PbAc 75 79.20 7 849
MEASUREMENT ENDPOINT
Blood
7.5
7.5
7.5
7.5
7.5
32.6
12.4
20.15
27.3
20.5
44.95
64.45 f b
41.25
38.45
19.75
Femur
1.5
0.5
0.5
0.5
0.5
2.55
2.2
1.4
3.7
4.25
4.5
5.55
6.6
6.5
4.2
Liver
10
10
10
10
85 | a
162
52
10
58
27
239
216
236
153
124
Kidney
21
10
40
25
91 | a
104
32
35
100
98
220
214
349
230
84
a a priori outlier determinations
b Outside 95% Prediction Intervals
-------
TABLE B-9 Best Curve Fit Parameters
BLOOD
BONE
LIVER
KIDNEY
PbAc Curve -
Exp
PbAc Curve - Linear
PbAc Curve - Linear
PbAc Curve - Linear
a
b
c
d
R2
AV Slag Curve -
a
b
c
d
R2
6.8 a 1.1
b 0.057
161.3 c
0.0045 d
0.0555 R2 0.766
Exp AV Slag Curve Linear
6.8 a 1.1
b 0.01
161.3 c
0.00088 d
0.670 R2 0.587
Equations Used
EXP Y=a+c*(1-expj-d*dose)J
LIN Y=a+b*dose
a 17.3
b 2.202
c
d
R2 0.71
AV Slag Curve Linear
a 17.3
b 0.243
c
d
R2 0.21
a
b
c
d
R2
AV Slag
a
b
c
d
R2
29.5
2.355
0.631
Curve -Linear
29.5
0.242
0.171
-------
TABLE B-10 Relative Bioavailability of Lead in Test Materials
End point
Blood
Kidney
Liver
Bone
Test Material
AV Slag
0.20
0.10
0.11
0.18
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
AV Slag
0.20 0.13
0.20 0.16
0.18
Absolute Bioavailability
Plausible Range
Preferred Range
Point Estimate
AV Slag
10% 6%
10% 8%
9%
-------
TABLE B-11 INTRALABORATORY DUPLICATES
RPD = Relative Percent Difference
RPD = 100'[Orig-Dup]/((Orig+Dup)/2
Non detects evaluated at 1/2 DL
Orig. pig number
824
824
824
824
824
824
824
824
824
824
849
849
849
849
849
849
849
849
849
849
853
853
853
853
853
853
853
853
853
853
824
849
853
824
849
853
824
849
853
jroup
10
10
10
10
10
10
10
10
10
10
7
7
7
7
7
7
7
7
7
7
3
3
3
3
3
3
3
3
3
3
10
7
3
10
7
3
10
7
3
material administered
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
AV Slag
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
IV
IV
IV
IV
IV
IV
IV
IV
IV
IV
AV Slag
PbAc
IV
AV Slag
PbAc
IV
AV Slag
PbAc
IV
dosage
225
225
225
225
225
225
225
225
225
225
75
75
75
75
75
75
75
75
75
75
50
50
50
50
50
50
50
50
50
50
225
75
50
225
75
50
225
75
50
day
-4
0
1
2
3
5
7
9
12
15
-4
0
1
2
3
5
7
9
12
15
-4
0
1
2
3
5
7
9
12
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
2.8
3.7
3.3
2.9
4
4.3
0.5
0.5
0.5
0.5
0.5
1,4
0.5
0.5
2
3.2
0.5
0.5
6.7
7.8
8.2
9.1
8.9
8.4
8.8
9.4
3.1
3.5
25.5
105
107
649
30
57
671
Original Value*
0.5
0.5
0.5
1
1.6
2.6
1.3
2.8
4.3
4.4
0.5
0.5
1.1
0.5
1
1
0.5
0.5
2.5
3.1
0.5
0.5
7.5
6.9
9
10.1
9
8
8.4
10
2.5
4.2
22.3
82
84
990
81
124
643
Average
0.5
0.5
0.5
0.75
2.2
3.15
2.3
2.85
4.15
4.35
0.5
0.5
0.8
0.5
0.75
1.2
0.5
0.5
2.25
3.15
0.5
0.5
7.1
7.35
8.6
9.6
8,95
8.2
8.6
9.7
2,8
3.85
23.9
93.5
95.5
819.5
55.5
90.5
657
RPD
0%
0%
0%
67%
-55%
-35%
-87%
-4%
7%
2%
0%
0%
75%
0%
67%
-33%
0%
0%
22%
-3%
0%
0%
11%
-12%
9%
10%
1%
-5%
-5%
6%
-21%
18%
-13%
-25%
-24%
42%
92%
74%
-4%
Avg RPD
0.013 BLOOD
-0.055 FEMUR
-0.024 KIDNEY
0.539 LIVER
-------
TABLE B-12 CDC STANDARDS
Sample ID
8.1
8.1
8.1
8.2
8.2
8.2
8.2
8.2
8.2
8.2
8.2
8.2
8.2
8.3
8.3
8.3
8.3
8.3
8.3
8.3
Dav Q
-4 <
0 <
1 <
-4
0
1
2
3
5
7
9
12
15
2
3
5
7
9
12
15
Averages
Measured
Low Std Med Std
1.0
1.0
1.0
3.8
3.8
3.8
3.6
4
3.5
3.6
3.3
3.3
3.1
2.1 3.5
High Std
12.6
12.6
14.9
15.5
13.9
12.7
14.1
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
13.8 NA
-------
TABLE B-13 INTERLABORATORY COMPARISON
Tag
Number
8-980271
8-980310
8-980315
8-980338
8-980370
8-980412
8-980401
8-980490
8-980446
8-980500
8-980526
8-980586
8-980568
8-980625
8-980605
Pig
Number
854
809
814
816
817
836
830
825
849
816
826
807
801
853
841
Group
9
5
9
4
6
1
5
3
7
4
8
2
4
3
5
Material
Administered
AV Slag
Control
AV Slag
IV
PbAc
IV
Control
IV
PbAc
IV
AV Slag
IV
IV
IV
Control
Dosage
75
0
75
100
25
0
0
50
75
100
25
25
100
50
0
Qualifier
CDC
U
u
U
u
EPA
<
<
<
<
<
<
<
<
CDC
1.5
0.7
2.2
14.5
2.8
0.6
0.6
9.1
0.6
12.8
0.6
10.2
13.0
10.6
0.6
Result
EPA
1.0
1.0
1.0
14.2
2.9
1.0
1.0
9.0
1.0
11.8
1.0
8.5
11.8
10.0
1,0
Average
1,3
0.9
1.6
14.4
2.9
0.8
0.8
9.1
0.8
12.3
0.8
9.4
12.4
10.3
0.8
RPD
-40
35
-75
-2
4
50
50
-1
50
-8
50
-18
-10
-6
50
-------
FIGURE B-1 PbAc Groups by Day
Raw Data - Phase II Experiment 8
m
a
a.
809
830
841
848
855
817
818
819
838
846
804
840
842
844
849
-------
Blood by Day - Raw Chart 6
FIGURE B-2 AV Slag Groups by Day
Raw Data - Phase II Experiment 8
03
.O
Q.
a802
A 826
* 828
-X 831
ฎ 851
-* - -806
- +- -814
823
X 547
-ซ-- 854
X 811
X822
^<824
X 837
ft 856
Page 1
-------
FIGURE B-3
THIS PAGE LEFT INTENTIONALLY BLANK
-------
IT
o
1
m
.a
a.
-4
FIGURE B-4 Group Mean PbB vs. Day
Raw Data
in
18 I
16 I
14 |
12 I
10 |
8 |
6 |
\ ^^ -JL J._ " Qr-- ฐ
* -2 0 2 4 6 8 10 12 14 1
Study Day
X 5 Control
ซ 6 PbAc 25
17 PbAc 75
8 AV Slag 25
9 AV Slag 75
-O-10AV Slag 225
6
-------
FIGURE B-5 COMPARISON OF DUPLICATE ANALYSES
PHASE II EXPERIMENT 8
5
D)
0)
3
1
CD
ง
10
9
8
7
6
5
4
3
2
1 -
0
Theoretical
y=1.00x+0.00
R2=1.00
Panel A
Blood Lead
Observed
y = 0.97x + 0.016
R2 = 0.99
456
Duplicate Value (ug/dL)
10
900
800
70ฐ
600 -
500
Panel B
Tissue Lead
Observed
y=1.06x-7.02
R2 = 0.98
Theoretical
y=1.00x-K).00
R2=1.00
200
300
400 500
Duplicate Value (ug/L)
600
700
800
900
-------
FIGURE B-6 CDCP CHECK SAMPLES FOR PHASE II EXPERIMENT 8
PANEL A ANALYSIS OF CDCP BLOOD LEAD CHECK SAMPLES
10
5
B>
_3_
ffi
n
Q.
-,
ie
12 -
9
6
3.8 <
3
1.0 4
I I 0
ฑ no A 15'5
A 13.9 A 14.1
A 12C 12.6 A 12.7
> 3-ซ 3.6 3.g 4 35 B 3.6 B 33 m 33 H 3 ^
> 1.ป 1.0
5 -3 -1 1 3 5 7 9 11 13 15
Study Day
4> Low Std
H Med Std
A High Std
Low Std
~ - - Med Std
High Std
PANEL B INTERLABORATORY COMPARISON BETWEEN EPA AND CDCP
6 8 10
CDCP PbB Results (ug/dL)
12
-------
Swine Study Phase II Exp 8
FIGURE B-7 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: PbAc Oral
ENDPOINT: Blood Lead ADC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
20
40 60
Dose (ug Pb/kg-day)
80
Parameters | Value
a
c
d
6.8
161.3
0.0045
Std. Error
fixed value
fixed value
0.0006
95% Confidence Limits
0.0031
0.0059
Adj R2
0.0555
"Generated using Table Curve 2D v. 3.0. Outliers represented by "+".
-------
Swine Study Phase II Exp 8
FIGURE B-8 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: AV Slag
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
QQ
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
c
d
Value
6.8
161.3
0.0009
Std. Error
fixed value
fixed value
9.30E-05
95% Confidence Limits
0.00068
0.0011
0.67
'Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 8
FIGURE B-9 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
7
6J
T3
0)
w C
CO O-
cn
4-
D)
-D 3H
CO
0)
0)
O
DO
2-
1-
MATERIAL: PbAc Oral
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
20 40 60
Dose (ug Pb/kg-day)
80
Parameters
a
b
Value
1.1
0.057
Std. Error
fixed value
0.0056
95% Confidence Limits
0.045
0.069
| Adj R2 0.766 |
'Generated using Table Curve 2D v. 3.0. Outliers represented by "+".
-------
Swine Study Phase II Exp 8
FIGURE B-10 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: AV Slag
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
ro
JQ
Q_
D)
(0
0)
_l
0)
c
o
m
4-
3-
2-
1-
T5o
Dose (ug Pb/kg-day)
300
Parameters | Value | Std. Error
a
b
1.1
0.010
fixed value
0.0014
95% Confidence Limits
-
0.0072
0.013
I AdjR2 0.587 |
"Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
Swine Study Phase II Exp 8
FIGURE B-11 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
300
I
250-
200 H
= 150J
CO
0)
100-
50-
0
0
MATERIAL: PbAcOral
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
20 40 60
Dose (ug Pb/kg-day)
Parameters
a
b
Value
17.3
2.202
Std. Error
fixed value
0.258
95% Confidence Limits
1.64
2.76
AdjR2 0.71
"Generated using Table Curve 2D v. 3.0. Outliers represented by "+".
-------
Swine Study Phase II Exp 8
FIGURE B-12 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
D)
.*:
!S
Q.
D)
T3
CO
0
160
140-
120-
100-
80-
60-
40-
20-
0
0
MATERIAL: AVSlag
ENDPOINT: Liver Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
17.3
0.243
Std. Error
fixed value
0.052
95% Confidence Limits
0.132
-
0.354
AdjR2
0.21
'Generated using Table Curve 2D v. 3.0. Outliers represented by "+
-------
Swine Study Phase II Exp 8
FIGURE B-13 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
400
MATERIAL: PbAcOral
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
20 40 60
Dose (ug Pb/kg-day)
Parameters) Value
a
b
29.5
2.35
Std. Error
fixed value
0.328
95% Confidence Limits
1.64
3.07
AdjR2
0.631
"Generated using Table Curve 2D v. 3.0. Outliers represented by "+"
-------
Swine Study Phase II Exp 8
FIGURE B-14 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
MATERIAL: AVSlag
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
I
I
a.
0)
TO
CO
CD
0)
-a
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
29.5
0.242
Std. Error
fixed value
0.059
95% Confidence Limits
0.118
0.367
\ AdjR2
0.171
'Generated using Table Curve 2D v. 3.0. Outliers represented by"+".
-------
SECTION C
STUDY 12
Oregon Gulch Tailings Sample
-------
TABLE C-1 BODY WEIGHTS AND ADMINISTERED DOSES, BY DAY
Body welghli were measured on days -1, 2. 5. ซ. 11, 14. Weight, for rXher days are estimated, based on linear irtenotolion between measu-ed values.
Croup ID*
1 1228
1 1238
2 1203
2 1213
2 1215
2 12U
2 1248
3 1227
3 1240
3 1243
3 1244
3 1255
4 1222
4 1225
4 1226
4 1241
4 1249
11 1204
11 1224
11 1238
11 1242
Day-1
8W ug Pb
ft" I"""
8.24 0.0
7.96 0.0
10.5 0.0
6.22 0.0
10,16 0.0
6.06 0.0
9.78 0.0
9.7 0.0
a.12 0.0
3 0.0
858 0.0
694 0-0
8.02 0.0
5.84 OH
6.28 0.0
752 00
8.2 0.0
708 0.0
796 0.0
7.48 0.0
7.38 0.0
DayO
BW ugPb
--ปป> ?ซ*>,
e.5 o.o
B.O 0.0
10.4 238.5
6.4 238.5
10.2 238.5
e-1 m*m
98 238.5
8.8 895.1
83 895,1
8.2 9951
89 9851
7.3 995.1
8.1 1748.7
6.1 174B.7
6.4 1748.7
7.6 1748.7
8.5 1748.7
7.3 18058
8.1 1905.6
7.8 mm*\-
7.5 1905.8
rtayl
BW ugPb
W Pซr da,
B.7 0.0
8.1 00
10.2 238.5
6.S 238.5
10.3 238.5
8.2 [119-3
9.9 238.5
9.9 695.1
8.4 895.1
84 8951
92 895.1
7.8 995.1
6.2 1748.7
6.4 1748.7
6.8 1748.7
7.8 1748,7
6.B 1748.7
7.5 1905.8
8.3 1905.8
6.0 19058
7.6 19058
Day 2
BW ugPb
8.93 0.0
8.2 0.0
10.08 238.5
6.7 238.5
10.34 238,5
6 28 | 238 5
9.9 238.5
10.04 695-f
8.58 695.1
868 685.1
8 S3 995.1
796 695.1
834 17487
8.82 1748,7
8.7 1748.7
7.88 1748.7
9.04 1748.7
7.7 1905.8
8.5 1905,8
8.32 1905.6
7.76 1905.8
Day 3
BW ygPb
9.3 0.0
8.4 0.0
10,8 241,5
7.0 241.5
10.6 241.5
6.5 | 350.8
10.1 241.5
10.2 747.3
8.9 747.3
9.0 747.3
9.8 747.3
8.1 747.3
7.3 1871.1
6.8 1871.1
7.1 1871.1
8.2 1871.1
9.4 1871.1
8.1 2040,8
8.6 2040.9
8.6 2040.8
8.1 2040.8
Day 4
3W ugPb
9.7 0.0
86 0.0
11.1 2415
73 2415
10.8 241.5
8.8 241.5
103 2415
10.5 747.3
9.1 747.3
9.3 7473
10,0 747.3
8.2 747.3
B.3 1871.1
7.0 1871.1
7.5 1871.1
8.5 1871.1
9.8 1871.1
8,5 20408
8.7 2040.8
8.9 2040.8
8.4 2040.8
DayS
BW ugPfc
11.5 0.0
10.02 0.0
8.82 0.0
11.64 241.5
7.64 241.5
11 241.5
7.08 241.5
10.48 241.5
10.68 747.3
9.4 747.3
9.56 747.3
10.2 747.3
8.3 747.3
9.3 1871.1
7.22 1871.1
7.88 1871.1
8.84 1871.1
10.24 1871.1
8.92 2040.8
8.14 2040.8
9.18 2040.8
8.74 2040.8
Day 8
BW ugPb
11.9 O.O
10.3 0.0
9.3 0.0
11.9 264.1
8.0 264.1
11.3 264.1
7.5 264.1
11.0 264.1
11.1 7S6.8
9.7 795.B
9.9 796.8
10.6 796.8
6.8 798.8
8.8 2191.6
7.5 2181.6
S-2 2181.6
9.3 2131.6
106 21816
B.2 2232.0
9.3 2232.0
9.5 2232.0
9.0 2232.0
Day 7
BW ugPb
12.2 0.0
10.5 0.0
9.9 CO
12.2 264.1
8.3 2841
11.6 264.1
7.9 2641
11.5 264.1
11.5 79S.S
10.0 796.8
10.2 796.8
11.0 798.8
9.3 79S.8
8.5 2181.6
7.8 2181.6
8.4 21(1.6
9.7 21S1.6
10.9 2181.6
9.5 2232.0
9.7 2232.0
9.9 22320
9.3 2232.0
Day8
BW ugPb
12.82 0.0
10.72 0.0
10 38 00
12.42 284.1
8,58 264.1
11.92 234.1
8.32 284.1
12.06 264.1
12.04 796.8
10.36 796.8
10.46 796.8
11.34 796.8
9 76 796 8
8.12 2181.6
8.1 2181.6
8.7 2131.6
102 2SS1.6
11.2 2131.6
9.74 2232.0
10.1 22320
102 22320
9.54 2232.0
Day 9
BW ugPb
13.1 0.0
11,0 0.0
10.4 0.0
12.7 291.6
83 291,6
12.2 291.6
87 291.6
12.5 291.6
125 834.4
10.8 884.4
10.8 884.4
119 8844
10.3 8*4.4
83 2309.4
8.4 2309.4
9.0 23094
10.7 2309.4
11.7 2309.4
10.3 2451.4
10.7 2451.4
10.8 2451.4
9.9 2451.4
Day 10
BW ugPb
13.5 0,0
11,3 0.0
10.4 0.0
13.0 291.6
9.0 291.8
12.4 291.9
9.0 291.6
12.9 291.6
13.0 884.4
11.3 684.4
1 1.2 884.4
125 8844
10.8 884,4
6.8 2309.4
6.7 2309,4
9.3 2309.4
1t.2 2309.4
12.2 2309.4
10.8 2451.4
11.2 2451.4
11.4 2451.4
10.3 2451.4
Day 11
BW ug Pb
13.94 0.0
11.54 0.0
10.48 D.O
1328 2916
9.2ซ 291.8
12.64 291.6
9.34 291.8
13 34 291 6
13.48 884.4
11.7 884.4
11.54 884.4
13.14 884,4
11.26 884.4
8.8 23094
8.98 2309.4
9.66 2309.4
11.76 2309,4
1274 23094
1138 24514
1182 24514
11.96 2491,4
10.66 2451 4
Day 12
BW ugPb
14.4 0,0
11.9 0.0
10.7 0.0
13.5 314.3
9.5 314.3
13.1 314.3
8.6 314,3
13.7 314.3
14.0 991.8
122 991.8
12.0 991.8
13.6 991.8
11.9 991.8
81 2562.3
93 25623
10.0 2562.3
12.2 2562.3
13.1 2562.3
12.0 2802.4
12.4 2802.4
12,6 2802.4
10.9 2802.4
Day 11
BW ugPb
14.9 C.O
12.2 0.0
10.9 0.0
13.6 314.3
9.7 314.3
13.7 314.3
B.8 314.3
14.1 314.3
14,5 991.8
12.6 9918
124 9918
14.1 991.8
12.4 991.B
9.4 2562.3
S.8 258J.3
10.4 2562.3
12.6 2562.3
13.5 2562.3
12.8 2802.4
13.0 S802.4
13.2 2802.4
11.2 2802 4
DayU
BW ugPb
15.38 0.0
1256 0.0
11,12 0.0
14.06 314.3
8.92 314.3
14.16 314.3
10.1 314.3
14.52 314.3
15.06 991.8
13.1 991.8
12.88 991.8
14.64 891.8
13.D4 891.8
8.72 25823
9.9 25623
10.72 2562.3
13.08 2562.3
1394 25623
13.24 2802.4
13.84 2802.4
13.82 28024
1152 28024
Day 15
BW ugPb
159 0.0
129 0.0
11,3 0.0
14,3 0,0
10,1 0.0
14 7 0.0
104 0.0
148 0.0
158 0.0
138 0.0
133 0,0
151 0.0
136 00
10.0 0.0
10.2 0.0
111 0.0
135 0.0
143 00
13 9 0.0
142 0.0
14.4 0.0
118 0.0
Shaded boxes show days In wHcfc administered doses were ingซsiad late
Days wNch required adjustment due to deviations In dosing (fe. Msstd doses)
Day 1 Rg 1217 - did no* eat pm dose unW neat morning. Doss adjusted to 50%
Day 2 Pig 1217 - Ate pm dose from Day f. Did nd ait pm dose for Day 2 until next day.
Day 3 Pig 121 ? - ซe pm dose from Day 2 in add-on to normal daily doses. Dose adjusted to account for previous day dougfeafl
-------
S*f iป Kudy Phase II Bcp 12
TABLE C-2
Body Weight Adjusted Doses
(Dose for Day/BW for Days
Group ID*
1 1205
1 1228
1 1236
2 1208
2 1213
2 1215
2 1217
2 1248
3 1227
3 1240
3 1243
3 1244
3 1255
4 1222
4 1225
4 1226
4 1241
4 1249
11 1204
11 1224
11 1238
11 1242
Day 0 Day 1
0 0
0 0
0 0
23.02 23.34
37.38 36.47
2334 2320
38.89 19.21
24.32 24.21
70.83 70.02
84.02 82.49
84.56 82.36
77.98 75.17
95.48 91.22
285.42 280,54
286.67 274.95
27238 266.57
22889 225.35
206,21 199.62
262.02 254.55
234,12 229.06
245,59 237.03
253.87 249.66
Day 2 Day 3
0 0
0 0
0 0
23.66 22.78
35.60 34.43
23.07 22.87
37.98 55.16
24.09 23,93
69.23 72.93
81.01 84.41
80.27 83.40
72.56 76.36
87.32 92.56
275.82 255.38
264.15 274.35
261.00 263.78
22192 228.18
193.44 198.21
247.50 251.74
224.21 236.93
22906 237.11
245,59 252.36
Day 4 Day 5
0 0
0 0
0 0
21.72 20.75
32.96 3161
22.40 21.95
3551 3421
23.48 23.04
71.49 70.10
81.88 79.50
80.70 78.17
74.78 7326
91.28 90.04
225.07 201.19
266.54 259.16
249.92 237.45
219.61 211.66
190.15 182.72
239.71 228.78
23385 23085
22947 22230
24256 233,50
Day6
0
0
0
22.19
3321
2336
35.31
23.98
71,65
8198
80.81
75.31
90,68
244,94
29036
267,57
23475
206,59
242.78
241.04
234.45
247.82
Day 7 Day 8
0 0
0 0
0 0
21.72 21.26
31.95 30.78
22.74 2216
33.43 31.74
22.87 21.86
68.81 66.18
79.36 76.91
78,43 76.18
7270 70,26
8592 81.64
256.26 268.67
27945 269.33
258,89 250.76
22383 213.88
200.51 194.79
235.77 229.16
230.58 220.99
226.37 218.82
240.69 233.96
Day 9 Day 10
0 0
0 0
0 0
22.95 22.44
33.11 32.28
23.98 2352
33,67 32.40
2333 2257
70,64 68.03
81.84 78.59
81.74 79.11
7407 70.53
86.20 82.19
276.69 269.37
275.15 265.86
256.03 247.26
215.43 205.46
197.16 188.88
238,31 226.28
229.67 217.96
227.26 215.54
247.28 238.31
Day 11 Day 12
0 0
0 0
0 0
21.96 23.21
31.49 33.15
2307 23.91
31.22 32.76
21.86 2289
65.61 70.81
75.59 81.52
76.64 82.74
67.31 7271
78.54 83.67
262.43 281,37
257.17 275.91
239.07 255,89
196.38 210.02
181.27 195.00
215.41 233.53
207.39 22551
204.96 22276
229.96 256.00
Day 13 Day 14
0 0
0 0
0 0
22.78 22.35
32 40 31 68
23,02 22.20
31,92 31.12
2225 21.65
68.24 6586
78.51 75.71
79.77 77.00
70.14 67.75
79.68 76.06
272.20 263.61
267.09 258.82
247.17 239,02
202.71 195.8S
189.24 183,81
222.06 211.66
215.02 205,45
212 30 202 78
249.47 243.26
Avg
Dose
0.00
0,00
0.0
224
332
23.0
343
23.1
694
80.2
80.1
72.7
86.2
261.3
271,0
2542
215.6
1938
236,0
225.5
2244
244.3
Target
Dose
""o
0
1
7S
7S
75
75
7S
225
22S
225
2SS
' 22'5I"
?2S
225
22S
% Avg
Target %
90
133
92
137
92 109
92
107
107
97
115 104
116
120
113
96
86 106
105
100
100
109 103
-------
Swine Study Phase II Experiment 12
TABLE C - 3 RAW AND ADJUSTED BLOOD LEAD DATA
PHASE II EXPERIMENT 12
pig number sample group material administered dosage qualifier result day source file MATRIX Adjusted Value (ug/dL)'
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
8-912-0143
8-912-0155
8-912-0138
8-912-0126
8-912-0156
8-912-0135
8-912-0146
8-912-0132
8-912-0124
8-912-0141
8-912-0172
8-912-0150
8-912-0129
8-912-0166
8-912-0122
8-912-0134
8-912-0140
8-912-0165
8-912-0120
8-912-0133
8-912-0148
8-912-0160
8-912-0211
8-912-0199
8-912-0229
8-912-0207
8-912-0218
8-912-0187
8-912-0222
8-912-0202
8-912-0181
8-912-0220
8-912-0194
8-912-0185
8-912-0204
8-912-0215
8-912-0209
8-912-0227
8-912-0192
8-912-0219
8-912-0197
8-912-0212
8-912-0189
8-912-0213
8-912-0250
8-912-0280
8-912-0288
8-912-0268
8-912-0285
8-912-0287
8-912-0257
8-912-0267
8-912-0259
8-912-0270
8-912-0244
8-912-0274
8-912-0249
8-912-0253
8-912-0258
8-912-0264
8-912-0269
8-912-0242
8-912-0266
8-912-0271
8-912-0236
8-912-0246
8-912-0333
8-912-0317
8-912-0295
8-912-0306
8-912-0297
8-912-0346
8-912-0318
8-912-0339
8-912-0304
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
0 <
0 <
0 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
0 <
0 <
0 <
25 <
25 <
25 <
25 <
25 <
75 <
75 <
75 <
75 <
75 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
225 <
0 <
0 <
0 <
25 <
25
25 <
25 <
25 <
75 <
75
75 <
75
75
225
225
225
225
225
225 <
225 <
225 <
225 <
0
0 <
0 <
25 <
25
25
25 <
25 <
75
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
1.3
1
1
1
1
2.2
1
1.6
1
1.9
2.5
1.2
3.8
2.1
1
1
1
1
1.5
1
1
1
1.4
2
1
1
1.2
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
-4 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
0 T960525B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
1 T960610B
T960610B
T960610B
T960610B
T960610B
T960610B
T960610B
T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
BLOOD
BLOOD
8LOQD
BLOPD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOQd
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LQQP
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LPOB
BLOOD
BLOOD
SLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOQD
BLOQD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOQD
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOQD
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLQOD
8LGOD
BLOQD
SLOaD
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.3
0.5
0.5
0.5
0.5
2.2
0.5
1.6
1
1.9
2.5
1.2
3.8
2.1
0.5
0.5
0.5
0.5
1.5
0.5
0.5
0.5
1.4
2
0.5
0.5
1.2
-------
Swine Study Phase II Experiment 12
pig number sample group material administered dosage qualifier result day source file MATRIX Adjusted Value lug/dL)'
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
8-912-0342
8-912-0321
8-912-0313
8-912-0308
8-912-0320
8-912-0298
8-912-0338
8-912-0312
8-912-0301
8-912-0292
8-912-0305
8-912-0303
8-912-0327
8-912-0360
8-912-0361
8-912-0381
8-912-0383
8-912-0349
8-912-0365
8-912-0378
8-912-0400
8-912-0382
8-912-0364
8-912-0386
8-912-0374
8-912-0363
8-912-0397
8-912-0351
8-912-0354
8-912-0348
8-912-0373
8-912-0362
8-912-0372
8-912-0370
8-912-0375
8-912-0434
8-912-0446
8-912-0445
8-912-0415
8-912-0432
8-912-0423
8-912-0442
8-912-0429
8-912-0414
8-912-0406
8-912-0457
8-912-0416
8-912-0407
8-912-0449
8-912-0453
8-912-0421
8-912-0409
8-912-0461
8-912-0412
8-912-0438
8-912-0405
8-912-0413
8-912-0515
8-912-0512
8-912-0518
8-912-0481
8-912-0467
8-912-0507
8-912-0487
8-912-0478
8-912-0517
8-912-0488
8-912-0490
8-912-0509
8-912-0516
8-912-0503
8-912-0506
8-912-0491
8-912-0497
8-912-0470
8-912-0473
8-912-0482
8-912-0464
8-912-0493
6
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
75
75
75
75
225
225
225
225
225
225 <
225 <
225 <
225 <
0 <
0 <
0 <
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
225
225
225 <
225 <
0 <
0 <
0 <
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
225
225 <
225
225
0 <
0 <
0
25 <
25
25
25
25
75
75
75
75
75
225
225
225
225
225
225 <
225
225
225
3.2
1.2
1.9
2.8
5.3
6
3.1
5.3
5.2
1
1
1
1
1
1
1
1.1
2.4
1.9
1
1.2
3.1
3.6
3
2.2
4.1
6.4
6.8
3.9
7.8
5.5
1.4
1.5
1
1
1
1
1
1.2
1
2.3
1
1
4.7
4.9
3.9
4.9
4.9
8.9
6.1
6.2
7.7
10.1
1.6
1
1.6
1.1
1
1
1.1
1
1.2
2.7
1.1
1.8
2.7
4.9
5.1
42
4.5
8.3
7.6
9.7
11.2
8.6
1
2.1
1.6
1
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
2 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
3 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
5 T960610B
7 T960617B
7 T960617B
7 T960617B
7 T960610B
7 T960610B
7 T960617B
7 T960617B
7 T960610B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960617B
7 T960610B
7 T960610B
7 T960617B
7 T960610B
7 T960617B
BLOOD
BLOOD
BLOOD
BLOOD
SLQOO
BLOOO
BLOOD
BLOOD
BLOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD.
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
8LQOD
BLOOD
BLOQD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
6LOQD
8LOQD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOQD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
8LQOD
8LOOD
BLOQD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
SLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOO
BLOOD
BLOOD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
8LOOO
BLOOD
3.2
1.2
1.9
2.8
5.3
6
3.1
5.3
5.2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.1
2.4
1.9
0.5
1.2
3.1
3.6
3
2.2
4.1
6.4
6.8
3.9
7.8
5.5
1.4
1.5
0.5
0.5
0.5
0.5
0.5
1.2
1
2.3
0.5
1
4.7
4.9
3.9
4.9
4.9
8.9
6.1
6.2
7.7
10.1
1.6
0.5
1.6
1.1
0.5
0.5
1.1
0.5
1.2
2.7
1.1
1.8
2.7
4.9
5.1
4.2
4.5
8.3
7.6
9.7
11.2
8.6
0.5
2.1
1.6
1
9 T960617B
BLOOD
0.5
-------
Swine Study Phase II Experiment 12
pig number sample group material administered dosage qualifier result day source file MATRIX Adjusted Value (ug/dL)"
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
8-912-0541
8-912-0570
8-912-0558
8-912-0562
8-912-0544
8-912-0545
8-912-0547
8-912-0529
8-912-0537
8-912-0560
8-912-0540
8-912-0554
8-912-0553
8-912-0575
8-912-0520
8-912-0557
8-912-0568
8-912-0519
8-912-0536
8-912-0542
8-912-0521
8-912-0585
8-912-0616
8-912-0603
8-912-0627
8-912-0628
8-912-0612
8-912-0605
8-912-0619
8-912-060.2
8-912-0623
8-912-0590
8-912-0595
8-912-0610
8-912-0631
8-912-0578
8-912-0608
8-912-0622
8-912-0614
8-912-0617
8-912-0587
8-912-0632
8-912-0606
8-912-0663
8-912-0679
8-912-0649
8-912-0674
8-912-0670
8-912-0642
8-912-0677
8-912-0661
8-912-0643
8-912-0660
8-912-0684
8-912-0680
8-912-0676
8-912-0650
8-912-0634
8-912-0656
8-912-0633
8-912-0636
8-912-0646
8-912-0666
8-912-0671
8-912-0647
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
0 <
0 <
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
225
225
225
225
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
225
225
225
225 <
0 <
0
0 <
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
225 <
225
225
225 <
1
1
2.2
1.8
2.4
1
2.5
2
6.2
4.7
3.2
5.3
8.7
7.6
9.1
9
8.8
1.3
2.4
2
1.3
1
1
1
1.7
2.6
2.3
1.4
2.6
2.7
5.4
3.3
3.7
5
8
10.4
7.9
10.8
8.8
1.3
1.8
2.3
1
1
1
1
1.9
3.1
1.3
2.5
1.9
2.3
5.5
6
6.3
5.3
8.8
8.4
10.1
9.4
5.2
1
1.9
3.3
1
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T9506178
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
9 T960617B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
1 2 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960617B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
12 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
15 T960622B
BLOOD
8LQQD
BLOOD
BLOOD
BLOOD
BLOOD
8LOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
81000
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BtOOD
8LOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
B1G00
81000
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LOOO
BLOOD
BLOOD
$LOQD
BLOOD
BLOOD
BLOOD
BLOOD
8LOOO
8LOQD
BLOOD
8LOOD
8LOQD
BLOOD
BLOOD
BLOOD
8LOOO
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
BLOOD
8LOOO
BLOOD
BLOOD
BLOOD
0.5
0.5
2.2
1.8
2.4
0.5
2.5
2
6.2
4.7
3.2
5.3
8.7
7.6
9.1
9
8.8
1.3
2.4
2
1.3
0.5
0.5
0.5
1.7
2.6
2.3
1.4
2.6
2.7
5.4
3.3
3.7
5
8
10.4
7.9
10.8
8.6
1.3
1.8
2.3
0.5
0.5
1
0.5
1.9
3.1
1.3
2.5
1.9
2.3
5.5
6
6.3
5.3
8.8
8.4
10.1
9.4
5.2
0.5
1.9
3.3
0.5
a Non-detects evaluated using 1/2 the quantitation limit; laboratory results (ug/L) converted to concentration in blood (ug/dL) by dividing by dilution factor of
-------
TABLE C-4 BLOOD LEAD OUTLIERS
Swine Study Phase II Exp 12
Flagged Data Points
JOutlier:
test
material
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
target
dosage
0
0
0
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
225
225
225
225
Actual
Dose* group ~
0.00 1
0.00 1
0.00 1
22.41 2
33.23 2
22.98 2
34.30 2
23.09 2
69.36 3
80.22 3
80.12 3
72.73 3
86.17 3
261.26 4
271.00 4
254.18 4
215.60 4
193.84 4
235.95 11
225.51 11
224.39 1 1
244.29 1 1
pig*
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
12S5
1222
1225
1226
1241
1249
1204
1224
1238
1242
BLOOD LEAD (ug/dL) BY DAY
-4
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
0.5
0.5
0.5
1.3
0.5
0.5
0.5
0.5
2.2
0.5
1.6
1
1.9
2.5
1.2
3.8
2.1
0.5
0.5
0.5
0.5
2
1.5
0.5
0.5
0.5
1.4
2
0.5
0.5
1.2
3.2
1.2
1.9
2.8
5.3
6
3.1
5.3
5.2
0.5
0.5
0.5
0.5
3
0.5
0.5
0.5
1.1
2.4
1.9
0.5
1.2
3.1
3.6
3
2.2
4.1
6.4
6.8
S3
7.8
5.5
1.4
1.5
0.5
0.5
5
0.5
0.5
0.5
1.2
1
2.3
0.5
1
4.7
4.9
3.9
4.9
4.9
8.9
6.1
6.2
7.7
191
1.6
0.5
1.6
1.1
7
0.5
0.5
1.1
0.5
1.2
2.7
1.1
1.8
2.7
4.9
5.1
4.2
4.5
8.3
7.6
9.7
11.2
8.6
0.5
2.1
1.6
1
9
0.5
0.5
0.5
2.2
1.8
2.4
0.5
2.5
2
6.2
4.7
32
5.3
8.7
7.6
9.1
9
8.8
1.3
24
2
1.3
12 15
0.5 0.5
0.5 1
0.5 0.5
1.7 1.9
2.6 3.1
2.3 1.3
1.4 2.5
2.6 1.9
2.7 S.3
54 5.5
3.3 6
3.7 6.3
5 5.3
8 8.8
10.4 8.4
7.9 10.1
10.8 9.4
8.B 5.2
1.3 0.5
1.8 1.9
2.3 3.3
0.5 0.5
* Average Time and Weight-Adjusted Dose for Each Pig
-------
Swine Study Phase II Exp 12
TABLE C-5 RATIONALE FOR PbB OUTLIER DECISIONS
NO OUTLIERS IDENTIFIED
-------
Swine Study Phase II Bcp 12
TABLE C-6 Area Under Curve Determinations
Calculated using interpolated values for missing or excluded data
AUC (ug/dL-days)
group
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
pig#
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
0-1
0.50
0.50
0.50
0.50
0.90
0.50
0.50
0.50
0.50
1.35
0.50
1.05
0.75
1.20
1.50
0.85
2.15
1.30
0.50
0.50
0.50
0.50
1-2
1.00
0.50
0.50
0.50
1.35
1.25
0.50
0.50
0.85
2.70
0.85
1.75
1.90
3.60
4.25
2.15
4.55
3.65
0.50
0.50
0.50
0.50
2-3
1.00
0.50
0.50
0.80
1.90
1.95
0.50
0.85
2.15
3.40
2.10
2.05
3.45
5.85
6.40
3.50
6.55
5.35
0.95
1.00
0.50
0.50
3-5
1.00
1.00
1.00
2.30
3.40
4.20
1.00
2.20
7.80
8.50
6.90
7.10
9.00
15.30
12.90
10.10
15.50
15.60
3.00
2.00
2.10
1.60
For Time Span Shown
5-7
1.00
1.00
1.60
1.70
2.20
5.00
1.60
2.80
7.40
9.80
9.00
9.10
9.40
17.20
13.70
15.90
18.90
18.70
2.10
2.60
3.20
2.10
7-9
1.00
1.00
1.60
2.70
3.00
5.10
1.60
4.30
4.70
11.10
9.80
7.40
9.80
17.00
15.20
18.80
20.20
17.40
1.80
4.50
3.60
2.30
9-12
1.50
1.50
1.50
5.85
6.60
7.05
2.85
7.65
7.05
17.40
12.00
10.35
15.45
25.05
27.00
25.50
29.70
26.40
3.90
6.30
6.45
2.70
12-15
1.50
2.25
1.50
5.40
8.55
5.40
5.85
6.75
7.50
16.35
13.95
15.00
15.45
25.20
28.20
27.00
30.30
21.00
2.70
5.55
8.40
1.50
AUC Total
(ug/dL-days)
8.50
8.25
8.70
19.75
27.90
30.45
14.40
25.55
37.95
70.60
55.10
53.80
65.20
110.40
109.15
103.80
127.85
109.40
15.45
22.95
25.25
11.70
-------
Swine Study Phase II Experiment 12
TABLE C - 7 TISSUE LEAD DATA
PHASE II EXPERIMENT! 12
pig number
ample group material administered dosage qualifier result day source file MATRIX Adjusted Value (ug/dL)'
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
1205
1228
1236
1208
1213
1215
1217
1248
1227
1240
1243
1244
1255
1222
1225
1226
1241
1249
1204
1224
1238
1242
8-912-0711
8-912-0710
8-912-0694
8-912-0706
8-912-0729
8-912-0732
8-912-0690
8-912-0739
8-912-0702
8-912-0713
8-912-0726
8-912-0737
8-912-0704
8-912-0698
8-912-0718
8-912-0721
8-912-0716
8-912-0701
8-912-0727
8-912-0708
8-912-0695
8-912-0691
8-912-0829
8-912-0806
8-912-0847
8-912-0810
8-912-0822
8-912-0836
8-912-0808
8-912-0832
8-912-0801
8-912-0835
8-912-0813
8-912-0814
8-912-0833
8-912-0819
8-912-0845
8-912-0830
8-912-0837
8-912-0848
8-912-0838
8-912-0851
8-912-0805
8-912-0817
8-912-0780
8-912-0772
8-912-0791
8-912-0752
8-912-0745
8-912-0799
8-912-0760
8-912-0754
8-912-0797
8-912-0773
8-912-0792
8-912-0789
8-912-0750
8-912-0769
8-912-0759
8-912-0794
8-912-0785
8-912-0768
8-912-0788
8-912-0748
8-912-0784
8-912-0749
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
1
1
1
2
2
2
2
2
3
3
3
3
3
4
4
4
4
4
11
11
11
11
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
Control
Control
Control
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
PbAc
Oregon Gulch
Oregon Gulch
Oregon Gulch
Oregon Gulch
0 <
0 <
0 <
25 <
25
25
25 <
25
75 <
75
75
75
75
225
225
225
225
225
225
225 <
225 <
225 <
0 <
0 <
0 <
25
25
25
25
25
75
75
75
75
75
225
225
225
225
225
225
225 <
225
225 <
0
0 <
0
25
25
25
25 <
25
75
75
75
75
75
225
225
225
225
225
225
225
225
225 <
2
2
2
2
4.1
4.6
2
2.3
2
6.5
10
10.5
7.1
18.6
18.2
24.1
8.7
7.5
2.2
2
2
2
2
2
2
3.1
2.8
5.3
1.8
270
10.7
14.5
11.7
11.5
12.2
20.1
24.9
31.7
26.4
33.3
2
2
4.3
2
2.5
2
3.2
2.5
2.3
2.8
2
2.1
7.4
14.6
9.5
11.9
10.3
29.3
22.7
36
22.8
60.6
2.6
2.2
5.1
2
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T9B0717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T980717F
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T96070BK
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960708K
15 T960625L
15 T960625L
15 T960625L
1 5 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
15 T960625L
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
FEMUR
F6MUR
FEMUR
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
WONEY
KIDNEY
KIDNEY
KIDNEY
KIDNEY
KJDNEY
KIDNEY
WDNEY
MONEY
KIDNEY
KIDNEY
KIDNEY
UVER
LIVER
LIVER
UVER
UVER
LIVER
UVER
LIVER
UVER
UVER
UVER
UVER
UVER
UVER
UVER
LIVER
UVER
UVER
LIVER
UVER
UV6R
UVER
0.5
0.5
0.5
0.5
2.05
2.3
0.5
1.15
0.5
3.25
5
5.25
3.55
9.3
9.1
12.05
4.35
3.75
1.1
0.5
0.5
0.5
10
10
10
31
28
53
18
2700
107
145
117
115
122
201
249
317
264
333
20
10
43
10
25
10
32
25
23
28
10
21
74
146
95
119
103
293
227
360
228
606
26
22
51
10
Non-defects evaluated using 1/2 the quantitation limit. Laboratory results (ug/L) converted to tissue concentrations by dividing by sample dilution factors
0.1 kg/L (liver, kidney) or 2 g/L {ashed bone). Final units are ug Pb/kg wet weight (liver, kidney) or ug Pb/g ashed bone (femur)
-------
Swine Study Phase II Exp 12
TABLE C-8 SUMMARY OF ENDPOINT OUTLIERS
| ~| Selected Outliers
test target Actual
material dosage Dose* group pig#
Control 0 0.00 1 1205
Control 0 0.00 1 1228
Control 0 0.00 1 1236
PbAc 25 22.41 2 1208
PbAc 25 33.23 2 1213
PbAc 25 22.98 2 1215
PbAc 25 34.30 2 1217
PbAc 25 23.09 2 1248
PbAc 75 69.36 3 1227
PbAc 75 80.22 3 1240
PbAc 75 80.12 3 1243
PbAc 75 72.73 3 1244
PbAc 75 86.17 3 1255
PbAc 225 261.26 4 1222
PbAc 225 271.00 4 1225
PbAc 225 254.18 4 1226
PbAc 225 215.60 4 1241
PbAc 225 193.84 4 1249
Oregon Gulch 225 235.95 11 1204
Oregon Gulch 225 225.51 11 1224
Oregon Gulch 225 224.39 11 1238
Oregon Gulch 225 244.29 11 1242
MEASUREMENT ENDPOINT
Blood
8.5
8.3
8.7
19.8
27.9
30.5
14.4
25.6
38.0
70.6
55.1
53.8
65.2
110.4
109.2
103.8
127.9
109.4
15.5
23.0
25.3
11.7
Femur
0.5
0.5
0.5
0.5
2.05
2.3
0.5
1.15
0.5
3.25
5
5.25
3.55
9.3
9.1
12.05
4.35
3.75
1.1
0.5
0.5
0.5
Liver
25.0
10.0
32.0
25.0
23.0
28.0
10.0
21.0
74.0
146.0
95.0
119.0
103.0
293.0
227.0
360.0
228.0
606.0 | b
26.0
22.0
51.0
10.0
Kidney
10.0
10.0
10.0
31.0
28.0
53.0
18.0
2700 | a
107.0
145.0
117.0
115.0
122.0
201.0
249.0
317.0
264.0
333.0 | b
20.0
10.0
43.0
10.0
a a priori outlier determinations
b Outside 95% Prediction Intervals
-------
TABLE C-9 Best Curve Fit Parameters
BLOOD
PbAc Curve -
a
b
c
d
R2
Exp
6.8
129
0.0066
0.949
BONE
PbAc Curve -
a
b
c
d
R2
Linear
0.62
0.0312
0.774
LIVER
PbAc Curve -
a
b
c
d
R2
Linear
14.7
1.049
0.903
KIDNEY
PbAc Curve -
a
b
c
d
R2
Linear
10,4
1.021
0.889
Equations Used
EXP Y=a+c*(1-exp(-d*dosej)
LIN Y=a+b*dose
-------
TABLE C-10 Relative Bioavailability of Lead in Test Material
Endpoint
Blood
Kidney
Liver
Bone
Test Material
Oregon Gulch
0.06
0.04
0.05
0.004
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
Oregon Gulch
0.06 0.03
0.06 0.05
0.06
Absolute Bioavailability
Plausible Range
Preferred Range
Point Estimate
Oregon Gulch
3%
3%
3%
2%
2%
-------
TABLE C-11 INTRALABORATORY DUPLICATES
RPD = Relative Percent Difference
RPD = 100*|Orig-Dup]/({Orig+Dup)/2
* Non detects evaluated at 1 /2 DL
Pig Number
1243
1251
1209
1236
1208
1217
1222
1203
1252
1212
1221
1246
1233
1216
1242
1226
1247
1229
1236
1215
1250
1241
1233
1203
1236
1225
1221
1241
1204
1224
1241
1239
1204
1227
1235
1246
1251
1207
grouf
3
5
6
1
2
2
4
6
8
9
10
10
5
10
11
4
6
7
1
2
5
4
5
6
1
4
10
4
11
11
4
10
11
3
7
10
5
8
i material administered dosage
PbAc
Galena
Galena
Control
PbAc
PbAc
PbAc
Galena
Palmerton Loc2
Pafmerton Loc2
Palmerton Loc2
Palmerton Loc2
Galena
Palmerton Loc2
Oregon Gulch
PbAc
Galena
Galena
Control
PbAc
Galena
PbAc
Galena
Galena
Control
PbAc
Palmerton Loc2
PbAc
Oregon Gulch
Oregon Gulch
PbAc
Palmerton Loc2
Oregon Gulch
PbAc
Galena
Palmerton Loc2
Galena
Palmerton Loc2
75
75
225
0
25
25
225
225
25
75
225
225
75
225
225
225
225
675
0
25
75
225
75
225
0
225
225
225
225
225
225
225
225
75
675
225
75
25
day matrix Duplicate Value*
-4 BLOOD
-4 BLOOD
-4 BLOOD
0 BLOOD
0 BLOOD
0 BLOOD
1 BLOOD
1 BLOOD
1 BLOOD
2 BLOOD
2 BLOOD
2 BLOOD
3 BLOOD
3 BLOOD
3 BLOOD
5 BLOOD
5 BLOOD
5 BLOOD
7 BLOOD
7 BLOOD
7 BLOOD
9 BLOOD
9 BLOOD
9 BLOOD
12 BLOOD
12 BLOOD
12 BLOOD
15 BLOOD
15 BLOOD
15 BLOOD
15 FEMUR
15 FEMUR
15 FEMUR
15 KIDNEY
15 KIDNEY
15 KIDNEY
15 LIVER
15 LIVER
0.5
0.5
0.5
0.5
0.5
0,5
3.1
0.5
0.5
0.5
4.2
3.3
0.5
6.9
0.5
5.2
0.5
0.5
0.5
2,6
0,5
10
0.5
0.5
0.5
8,7
7.6
10.8
1.8
2.3
15.05
6.65
1.4
93
10
170
10
27
Original Value*
0.5
0.5
0.5
0,5
0.5
0.5
1.9
0.5
0.5
0.5
4
2.2
0.5
5.8
0.5
6.2
0.5
0.5
1.1
2.7
1.1
9
0.5
0.5
0.5
10.4
6.6
9.4
0.5
1.9
4.35
5.8
1.1
107
20
225
10
28
Average
0.5
0.5
0.5
0.5
0.5
0.5
2.5
0.5
0.5
0.5
4.1
2.75
0.5
6.35
0.5
5.7
0.5
0.5
0.8
2.65
0.8
9.5
0.5
0.5
0.5
9.55
7.1
10.1
1.15
2.1
9.7
6.225
1.25
100
15
197,5
10
27.5
RPD
0%
0%
0%
0%
0%
0%
-48%
0%
0%
0%
-5%
-40%
0%
-17%
0%
18%
0%
0%
75%
4%
75%
-11%
0%
0%
0%
18%
-14%
-14%
-113%
-19%
-110%
-14%
-24%
14%
67%
28%
0%
4%
Avg RPD
-7% BLOOD
-49% FEMUR
36% KIDNEY
2% LIVER
-------
TABLEC-12 CDC STANDARDS
Sample ID Day Q
12.1 -4 <
12.1 0
12.1 1 <
12.1 3
12.1 5
12.1 12
12.2 -4
12.2 1
12.2 2
12.2 3
12.2 7
12.2 9
12.2 15
12.3 0
12.3 2
12.3 5
12.3 7
12.3 9
12.3 12
12.3 15
Averages
Measured*
Low Std Med Std Hiqh Std
1
1
1
1.8
1.6
1.7
1.35
4.6
4.8
3.9
4.9
4.4
5.3
4
4.56
16.5
16.3
15.1
15,4
17.4
11.4
16.1
Nominal
Low Std Med Std Hiqh Std
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
1.7 4.8 14.9
15.46
Mean ratios
0.79
0.95
1.04
Non-detects evaluated at the detection limit
-------
TABLE C-13 INTERLABORATORY COMPARISON
Tag
Number
8-912-0121
8-912-0122
8-912-0177
8-912-0178
8-912-0179
8-912-0234
8-912-0235
8-912-0236
8-912-0291
8-912-0292
8-912-0293
8-912-0348
8-912-0349
8-912-0350
8-912-0405
8-912-0406
8-912-0407
8-912-0462
8-912-0463
8-912-0464
8-912-0519
8-912-0520
8-912-0521
8-912-0576
8-912-0577
8-912-0578
8-912-0633
8-912-0634
8-912-0635
P'g
Number
1207
1225
1253
1232
21217
1210
1229
1238
1245
1204
1221
1241
1213
12.1
1238
1240
1255
1251
1223
1238
1204
1226
1242
21236
1203
1225
1241
1225
1247
Group
8
4
5
9
2
g
7
11
8
11
10
4
2
-
11
3
3
5
8
11
11
4
11
1
6
4
4
4
6
Material
Administered
Oregon Gulch
Palmerton Loc 2
PbAc
Galena
Palmerton Loc 2
PbAc
Palmerton Loc 2
Galena
Oregon Gulch
Palmerton Loc 2
Oregon Gulch
Palmerton Loc 2
PbAc
PbAc
-
Oregon Gulch
PbAc
PbAc
Galena
Palmerton Loc 2
Oregon Gulch
Oregon Gulch
PbAc
Oregon Gulch
Control
Galena
PbAc
PbAc
PbAc
Galena
Dosage
25
225
75
75
25
75
675
225
25
225
225
225
25
225
75
75
75
25
225
225
225
225
0
225
225
225
225
225
Qua!
CDC
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
ifier
| EPA
<
<
<
<
<
<
<
<
<
<
<
<
<
<
<
CDC
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0.6
0,6
0.6
0.6
2.4
8.2
1
0.6
0.6
4.3
3.5
0.6
0.6
0.6
0.6
7.9
0.6
0.6
0.6
9.3
9.8
8
0.6
Result
EPA
1
1
1
1
1
1
1
1
1
1
1
4
7.8
2.4
1.8
1.6
4.9
4.9
1
1
1.6
1.3
9.1
1.3
1
1.2
10.4
9.4
8,4
1
0.8
0.8
0.8
0.8
0,8
0.8
0.8
0.8
0.8
0,8
0.8
3.2
8
1.7
1.2
1.1
4.6
4.2
0.8
0.8
1.1
0.95
8.5
0.95
0.8
0.9
9.85
9.6
8.2
0.8
50
50
50
50
50
50
50
50
50
50
50
50
-5
82
100
91
13
33
50
50
91
74
14
74
50
67
11
-4
5
50
-------
FIGURE C-1 PbAc Groups by Day
Raw Data
I
m
.o
Q.
-------
FIGURE C-2 Oregon Gulch Groups
Raw Data
10
-1204
-1224
-1238
-1242
-2
2
H 6-
68
Study Day
10
12 14 16 18
-------
FIGURE C-3
THIS PAGE LEFT INTENTIONALLY BLANK
-------
O)
m
Q.
FIGURE C-4 Group Mean PbB By Day
Raw Data
1 control
m ' 2 PbAc 25
A - 3 PbAc 75
X ป 4 PbAc 225
11 Oregon Gulch 225
-------
12
10
2 -
0
FIGURE C-5 COMPARISON OF DUPLICATE ANALYSES
PHASE II EXPERIMENT 12
Panel A
Blood Lead
Observed
y = 0.96x + 0.034
R2 = 0.99
10
12
Duplicate Value (ug/dL)
Panel B
Tissue Lead
40
60
80 100
Duplicate Value (ug/L)
120
140
160
180
Blind random duplicates submitted at a 5% rate to EPA laboratories to provide
a measure of analytical precision (reproducibility)
-------
FIGURE C-6 CDCP CHECK SAMPLES
PHASE II EXPERIMENT 12
2"
5
0)
2
Q.
-
PANEL A ANALYSIS OF CDCP BLOOD LEAD CHECK SAMPLES
"0
18 -
16 -
14
A Low Std
0 MedStd 12-
High Std
Med Std
6 -
U 1.D 4
2 -
A 1 i
i 0
17.4
' 16'5 I" 16.1
+ 1*1 15-4
11.4
a 40 O 19 H 5.3
Q 3.9 0 4.4 B 4
MAI X ' ^
5-1 3 7 11 15
Study Day
PANEL B INTERLABORATORY COMPARISON BETWEEN EPA AND CDCP
15
5
D)
i"
I
2
a.
12 -
9
Observed
y - 0.98x + 0.65
Theoretical
y-1.00x + 0.00
R2 - 1.00
6 9
CDCP PbB Results (ug/dL)
12
15
-------
Swine Study Phase II Exp 12
FIGURE C-7 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
CO
9
D)
O
<
T3
CO
.3
T3
O
_O
CO
150
125-
100-
MATERIAL: PbAc
ENDPOINT: Blood Lead AUC
BEST FIT EQUATION: Y=a+c*(1-exp(-d*X))
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
c
d
Value
6.8
129
0.0066
Std. Error
fixed value
fixed value
0.0005
95% Confidence Limits
0.0056
0.0076
AdjR2
0.949
Generated using Table Curve 2D v. 3.0. Outliers represented by "+"
-------
Swine Study Phase II Exp 12
FIGURE C-8 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
CD
_g>
.Q
D.
D)
CD
CD
CD
o
CO
15
12.5-
10-
7.5-
5-
2.5-
0
MATERIAL: PbAc
ENDPOINT: Bone Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters | Value
a
b
0.62
0.031
Std. Error
fixed value
0.0029
95% Confidence Limits
0.025
0.037
AdjFT
0.774
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
-------
Swine Study Phase II Exp 12
FIGURE C-9 BEST FIT CURVE WITH 95% PREDICTION INTERVALS*
o_
D)
T5
co
-------
Swine Study Phase II Exp 12
FIGURE C-10 BEST FIT CURVE WITH 95% PREDICTION JNTERVALS*
CD
.0
0.
0)
a
CO
CD
3000
2500-
2000-
1500-
1000-
500-
MATERIAL: PbAc
ENDPOINT: Kidney Lead
BEST FIT EQUATION: Y=a+b*X
100 200
Dose (ug Pb/kg-day)
300
Parameters
a
b
Value
10.4
1.021
Std. Error
fixed value
0.064
95% Confidence Limits
0.886
1.157
AdjR2
0.889
Generated using Table Curve 2D v. 3.0. Outliers represented by"+"
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