Audited DRAFT Final Report

METABOLISM AND PHARMACOKINETICS OF DIISOPROPYL ETHER IN MALE AND FEMALE
RATS: PILOT STUDY

SUBMITTED TO:

Section 211(b) Research Group

American Petroleum Institute 

1220 L Street NW 

Washington, DC 20005

TESTING FACILITY:

Discovery Sciences

RTI International*

3040 Cornwallis Road

P.O. Box 12194

Research Triangle Park, NC 27709-2194

RTI Protocol:	RTI-934

RTI Study Code:	Rt05-934

RTI Report No.	RTI/0209408.001

March 24December 10, 2013January 11, 2015



Timothy R. Fennell, Ph.D.

Study Director



*RTI International is a trade name of Research Triangle Institute.

SUMMARY

This study evaluated the pharmacokinetics and disposition of diisopropyl
ether (DIPE) in male and Fischer 344 rats following nose only exposure. 
Three separate studies were conducted.  

In Study A, nose-only inhalation exposure of jugular-vein cannulated
male and female Fischer 344 rats to 3600 ppm DIPE for 6 hours (actual
concentration 3643 ± 177 ppm) was conducted, and serial blood samples
were obtained up to 16 24 h following exposure.  Headspace GC-MS
analysis of DIPE, isopropanol and acetone was conducted on the blood
samples.  DIPE was less than the limit of quantitation (LOQ) in
preexposure samples.  DIPE accumulated rapidly during the 6 hours of
exposure, and rapidly declined after the exposure.  There was little
difference in blood levels at peak concentration between males and
females.  All samples were below LOQ by 16 hr. In the male rats,
isopropanol was below LOQ in preexposure samples, all three samples
collected at 5 min, and in one of the three collected at 10 min.  The
concentration of isopropanol rose steadily during the exposure, and then
declined gradually.  In male rats, blood concentrations of isopropanol
reached peak concentrations at approximately twice those of female rats.
 All samples were below LOQ by 16 hr.  In the female rats, isopropanol
was below LOQ in preexposure samples, and all samples collected at 5,
10, and 15 min.  The concentration of isopropanol rose steadily during
the exposure, and then declined gradually.  In male rats, blood
concentrations of isopropanol peaked at approximately twice those of
female rats.  All samples were below LOQ by 16 hr.  In male and female
rats, acetone was above LOQ in 5 of the 6 preexposure samples.  Acetone
levels in both male and female rats rose steadily during the exposure,
and in males continued to rise following exposure until 8 hr following
the initiation of exposure.  In females, the acetone levels were
approximately the same between 6 and 8 hours following the exposure, and
then declined rapidly reaching preexposure levels by 16 hrs in females. 
The concentration achieved in males exceeded the range of the
calibration curve, and for samples obtained between 6 hours and 10 hours
are estimated by linear extrapolation of the calibration curve.  The
peak concentrations of acetone achieved in male rats were approximately
50% higher than those in female rats,  and for isopropanol the peak
concentrations in males were almost twice those in females .  Male rats
reached preexposure levels by 24 hours.  Non-compartmental
pharmacokinetic analysis of  the mean concentrations of each analyte was
conducted using WinNonlin.  DIPE was eliminated with a half life of
Pharmacokinetic analysis of DIPE indicated a half life of 0.92 h in male
rats, and 0.76 h in female rats.  Isopropanol had an apparent half life
of 1.16 and 1.23 h in male and female rats, respectively.  Acetone had
an apparent half life of 2.31 and 2.32 h in male and female rats,
respectively.  

In Study B, four male Fischer 344 rats were exposed to [2-14C]
diisopropyl ether in a nose-only inhalation system at a target
concentration of 3600 ppm for 6 hours (actual concentration 3529 ( 40
ppm).  Following exposure, the 4 rats were euthanized immediately and
the radioactivity in the carcass was determined by digestion and
scintillation counting (Group 2, Study B).  In Study C, four male
Fischer 344 rats were exposed to a mixture of 13C6 and [2-14C]
diisopropyl ether in a nose-only inhalation system at a target
concentration of 3600 ppm for 6 hours (actual concentration 3334 ( 99
ppm, actual exposure time 5 hours and 40 minutes).  The rats were
transferred to all-glass metabolism cages, and urine, feces, exhaled CO2
and exhaled volatiles were collected for seven days (Group 3, Study C). 
After seven days, the rats were euthanized and the radioactivity
remaining in the carcass was determined by digestion and scintillation
counting.  Radioactivity was eliminated primarily as exhaled volatiles
(70 % of the recovered radioactivity).  Approximately 20 % was recovered
as 14CO2. Small amounts of radioactivity were recovered in urine (5% of
the recovered radioactivity).  A lesser amount was recovered (1%) in
feces, and 2.6% in carcass at 7 days.   

Based on the recovered radioactivity, the estimated dose in the rats in
Group 2 was 371 373 ( 8 mg/kg, and in Group 2 3 was 299 318 ( 7 8 mg/kg.
 Elimination of radioactivity was rapid, with 93.7% and 95.5% of the
radioactivity recovered within 24 h and 48 h, respectively, following
the end of exposure.  

The objectives of the study to develop a system for inhalation exposure
to DIPE and rr to develop analytical methods for the analysis of DIPE,
acetone and isopropanol were achieved.  Additional objectives achieved
were characterization of the kinetics of DIPE, acetone and isopropanol
in blood from rats exposed to 3600 ppm DIPE by inhalation for 6 hours,
and  analysis of the disposition of radioactivity conducted following
exposure to [2-14C] DIPE, and 13C6 and [2-14C] DIPE.  The objective of
characterizing urinary metabolites was not pursued because of the low
excretion of radioactivity in urine.

Quality Assurance Statement

Laboratory GLP Compliance Statement

This study was carried out in compliance with the EPA Good Laboratory
Practices (GLP) Standards for Inhalation Exposure Health Effects
Testing, 40 CFR part 79, subpart F § 79.60.  

The prestudy exposure system method development was completed at CIIT
Centers for Health Research and was not conducted under GLPs.  The
analysis of port to port variability of the nose only inhalation system
was conducted as part of this prestudy conduct, and was not repeated as
part of the GLP verification of system performance.  

The method of synthesis of the test chemical diisopropyl ether and
[2-14C]-diisopropyl ether, or their location was not available at the
time of conduct of the study.   Information on the method of synthesis
of [2-14C]-diisopropyl ether has been obtained from the vendor. 
However, the The suppliers of unlabeled diisopropyl ether has have been
unable to provide information on the methods of synthesis.  

There were no significant deviations (Appendix A) that would affect the
integrity or quality of the study or the interpretation of the results. 
Specimens, as applicable, raw data, copies of the inhalation data, and
the final report generated as a result of this study are archived at RTI
International.

						

Timothy R. Fennell, Ph.D.		Date

Study Director

						

Derek Swick  Ph.D.		Date

Sponsors Representative

Table of Contents

Page

  TOC \o "3-3" \h \z \t "Heading 1,1,Heading 2,2"    HYPERLINK \l
"_Toc351999782"  1.0  	Introduction	  PAGEREF _Toc351999782 \h  1  

  HYPERLINK \l "_Toc351999783"  2.0  	Objectives and Protocol	  PAGEREF
_Toc351999783 \h  1  

 HYPERLINK \l "_Toc351999784" 3.0  	Materials and Methods	  PAGEREF
_Toc351999784 \h  221  

 HYPERLINK \l "_Toc351999785" 3.1  	Test Substance	  PAGEREF
_Toc351999785 \h  221  

  HYPERLINK \l "_Toc351999786"  3.1.1  	Nonradiolabeled diisopropyl
ether	  PAGEREF _Toc351999786 \h  2  

  HYPERLINK \l "_Toc351999787"  3.1.2  	(U-13C6)-labeled diisopropyl
ether	  PAGEREF _Toc351999787 \h  2  

  HYPERLINK \l "_Toc351999788"  3.1.2  	[2-14C]-labeled diisopropyl
ether	  PAGEREF _Toc351999788 \h  2  

  HYPERLINK \l "_Toc351999789"  3.2  	Reference Substances	  PAGEREF
_Toc351999789 \h  3  

  HYPERLINK \l "_Toc351999790"  3.3  	Test System	  PAGEREF
_Toc351999790 \h  3  

  HYPERLINK \l "_Toc351999791"  3.4  	Test Chemical Preparation and
Analysis	  PAGEREF _Toc351999791 \h  4  

  HYPERLINK \l "_Toc351999792"  3.5  	Inhalation Exposure	  PAGEREF
_Toc351999792 \h  5  

  HYPERLINK \l "_Toc351999793"  3.5.1 Exposure Analysis	  PAGEREF
_Toc351999793 \h  6  

  HYPERLINK \l "_Toc351999794"  3.6  	Collection of Samples	  PAGEREF
_Toc351999794 \h  6  

  HYPERLINK \l "_Toc351999795"  3.6.1	Blood Sample Collection	  PAGEREF
_Toc351999795 \h  6  

 HYPERLINK \l "_Toc351999796" 3.7.1	Excreta	  PAGEREF _Toc351999796 \h 
776  

  HYPERLINK \l "_Toc351999797"  3.6.2	Carcass	  PAGEREF _Toc351999797 \h
 7  

  HYPERLINK \l "_Toc351999798"  3.6.2	Tissues	  PAGEREF _Toc351999798 \h
 7  

  HYPERLINK \l "_Toc351999799"  3.8  	Analysis of Blood Samples for
DIPE, Isopropanol, and Acetone	  PAGEREF _Toc351999799 \h  8  

  HYPERLINK \l "_Toc351999800"  3.8  	Analysis of Samples for Total
Radioactivity	  PAGEREF _Toc351999800 \h  8  

  HYPERLINK \l "_Toc351999801"  3.8.1	Excreta	  PAGEREF _Toc351999801 \h
 98  

  HYPERLINK \l "_Toc351999802"  3.8.2	Tissues and Carcass	  PAGEREF
_Toc351999802 \h  9  

  HYPERLINK \l "_Toc351999803"  3.8.3  Exhaled Breath Traps	  PAGEREF
_Toc351999803 \h  9  

  HYPERLINK \l "_Toc351999804"  3.8.4  Exhaled Volatiles Traps	  PAGEREF
_Toc351999804 \h  9  

  HYPERLINK \l "_Toc351999805"  3.9  	Data Collection and Reporting	 
PAGEREF _Toc351999805 \h  9  

  HYPERLINK \l "_Toc351999806"  4.0  	Results	  PAGEREF _Toc351999806 \h
 10  

  HYPERLINK \l "_Toc351999807"  4.1  	Analysis of Radiolabeled Test
Chemical Identity and Purity	  PAGEREF _Toc351999807 \h  10  

  HYPERLINK \l "_Toc351999808"  4.2  	Test Chemical Formulation	 
PAGEREF _Toc351999808 \h  10  

  HYPERLINK \l "_Toc351999809"  4.3  	Inhalation exposure	  PAGEREF
_Toc351999809 \h  10  

 HYPERLINK \l "_Toc351999810" 4.4  	DIPE, Acetone and Isopropanol in
Blood During and  Following Exposure	  PAGEREF _Toc351999810 \h  111110 


  HYPERLINK \l "_Toc351999811"  4.5  	Radioactivity Retained Following
Exposure	  PAGEREF _Toc351999811 \h  12  

  HYPERLINK \l "_Toc351999812"  4.6  	Excretion of Radioactivity	 
PAGEREF _Toc351999812 \h  12  

  HYPERLINK \l "_Toc351999813"  5.0  	Discussion	  PAGEREF _Toc351999813
\h  13  

 HYPERLINK \l "_Toc351999814" 6.0  	References	  PAGEREF _Toc351999814
\h  151514  

 HYPERLINK \l "_Toc351999815" 7.0  	RECORDS and Reports	  PAGEREF
_Toc351999815 \h  151514  

 HYPERLINK \l "_Toc351999816" 8.0  	Storage of Records and Biological
Samples	  PAGEREF _Toc351999816 \h  151514  

 HYPERLINK \l "_Toc351999817" 9.0  	REGULATORY COMPLIANCE	  PAGEREF
_Toc351999817 \h  161615  

 HYPERLINK \l "_Toc351999818" 10.0  	STUDY PARTICIPANTS	  PAGEREF
_Toc351999818 \h  161615  

 List of Tables

Page

  TOC \h \z \t "Table Title" \c "Table"    HYPERLINK \l "_Toc419387375" 
Table 1.	  Male and Female Fischer 344 Rats Used on the Study	  PAGEREF
_Toc419387375 \h  17  

  HYPERLINK \l "_Toc419387376"  Table 2.	  Exposure Conditions and
Concentration of DIPE, Study A.	  PAGEREF _Toc419387376 \h  18  

  HYPERLINK \l "_Toc419387377"  Table 3.	  Exposure Conditions and
Concentration of [2-14C]DIPE/DIPE, Study B.	  PAGEREF _Toc419387377 \h 
19  

  HYPERLINK \l "_Toc419387378"  Table 4.	  Exposure Conditions and
Concentration of [2-14C]DIPE/13CDIPE, Study C.	  PAGEREF _Toc419387378
\h  20  

  HYPERLINK \l "_Toc419387379"  Table 5.	  Concentration of DIPE in
blood from male and female rats exposed to 3600 ppm DIPE.	  PAGEREF
_Toc419387379 \h  21  

  HYPERLINK \l "_Toc419387380"  Table 6.	  Concentration of Isopropanol
in blood from male and female rats exposed to 3600 ppm DIPE.	  PAGEREF
_Toc419387380 \h  22  

  HYPERLINK \l "_Toc419387381"  Table 7.	  Concentration of Acetone in
blood from male and female rats exposed to 3600 ppm DIPE.	  PAGEREF
_Toc419387381 \h  23  

  HYPERLINK \l "_Toc419387382"  Table 8.	  Pharmacokinetic Analysis of
DIPE, Isopropanol and Acetone in male and female rats exposed to 3600
ppm DIPE.	  PAGEREF _Toc419387382 \h  24  

  HYPERLINK \l "_Toc419387383"  Table 9.	  Total Recoverya of
Radioactivity following Exposure to 3600 ppm [2-14C]DIPE/DIPE	  PAGEREF
_Toc419387383 \h  25  

  HYPERLINK \l "_Toc419387384"  Table 10.	  Recovery of Radioactivity in
Carcass following Exposure to 3600 ppm [2-14C]DIPE/DIPE (Group 2)	 
PAGEREF _Toc419387384 \h  26  

  HYPERLINK \l "_Toc419387385"  Table 11.	  Recovery of Radioactivity in
Excreta and Carcass following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE
(Group 3)	  PAGEREF _Toc419387385 \h  27  

  HYPERLINK \l "_Toc419387386"  Table 12.	  Recovery of Radioactivity in
Urine following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	 
PAGEREF _Toc419387386 \h  28  

  HYPERLINK \l "_Toc419387387"  Table 13.	  Recovery of Radioactivity in
Feces following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	 
PAGEREF _Toc419387387 \h  29  

  HYPERLINK \l "_Toc419387388"  Table 14.	  Recovery of Radioactivity in
CO2 Trap 1  following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group
3)	  PAGEREF _Toc419387388 \h  30  

  HYPERLINK \l "_Toc419387389"  Table 15.	  Recovery of Radioactivity in
CO2 Trap 2 following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)
  PAGEREF _Toc419387389 \h  31  

  HYPERLINK \l "_Toc419387390"  Table 16.	  Recovery of Radioactivity in
Exhaled VOC Trap 1 following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE
(Group 3)	  PAGEREF _Toc419387390 \h  32  

  HYPERLINK \l "_Toc419387391"  Table 17.	  Recovery of Radioactivity in
Exhaled VOC Trap 2 following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE
(Group 3)	  PAGEREF _Toc419387391 \h  33  

  HYPERLINK \l "_Toc419387392"  Table 18.	  Cumulative Recovery of
Radioactivity in Excreta and Carcass following Exposure to 3600 ppm
[2-14C]DIPE/13C6DIPE (Group 3)	  PAGEREF _Toc419387392 \h  34  

  HYPERLINK \l "_Toc419387393"  Table 19.	  Recovery of Radioactivity in
Tissues from Rat CM-02 following Exposure to 3600 ppm
[2-14C]DIPE/13C6DIPE (Group 3)	  PAGEREF _Toc419387393 \h  35  

  HYPERLINK \l "_Toc419387394"  Table 20.	  Normalized Recovery of
Radioactivity in Exposure B and C (Groups 2 and 3).	  PAGEREF
_Toc419387394 \h  36  

  HYPERLINK \l "_Toc419387395"  Sample Naming and Abbreviations	 
PAGEREF _Toc419387395 \h  2  

  HYPERLINK \l "_Toc419387396"  In the tables of raw data values in this
appendix, the table headings are derived from the conventions of sample
naming used in the Debra( system.  These are explained below.  Example
calculations and formulae are provided in Appendix G.	  PAGEREF
_Toc419387396 \h  2  

  HYPERLINK \l "_Toc419387397"  Table 1.  Preparation of 14C DIPE
Formulation (Feedstock) for Inhalation Exposure	  PAGEREF _Toc419387397
\h  4  

  HYPERLINK \l "_Toc419387398"  14C DIPE for Study B	  PAGEREF
_Toc419387398 \h  4  

  HYPERLINK \l "_Toc419387399"  Table 1 (contd).  Preparation of 14C
DIPE Formulation (Feedstock) for Inhalation Exposure	  PAGEREF
_Toc419387399 \h  5  

  HYPERLINK \l "_Toc419387400"  13C/14C DIPE For Study C	  PAGEREF
_Toc419387400 \h  5  

  HYPERLINK \l "_Toc419387401"  Table 2.  Recovery of Radioactivity in
Samples from Group B.	  PAGEREF _Toc419387401 \h  6  

  HYPERLINK \l "_Toc419387402"  Table 3.  Total Recovery of
Radioactivity in Samples from Group B.	  PAGEREF _Toc419387402 \h  7  

  HYPERLINK \l "_Toc419387403"  Table 4.  Recovery of Radioactivity in
Urine from Group C.	  PAGEREF _Toc419387403 \h  8  

  HYPERLINK \l "_Toc419387404"  Table 4 (contd).  Recovery of
Radioactivity in Urine from Group 2.	  PAGEREF _Toc419387404 \h  9  

  HYPERLINK \l "_Toc419387405"  Table 5.  Recovery of Radioactivity in
Feces from Group C.	  PAGEREF _Toc419387405 \h  10  

  HYPERLINK \l "_Toc419387406"  Table 5 (contd).  Recovery of
Radioactivity in Feces from Group C.	  PAGEREF _Toc419387406 \h  11  

  HYPERLINK \l "_Toc419387407"  Table 6.  Recovery of Radioactivity in
CO2 Trap 1 from Group C.	  PAGEREF _Toc419387407 \h  12  

  HYPERLINK \l "_Toc419387408"  Table 6 (contd).  Recovery of
Radioactivity in CO2 Trap 1 from Group C.	  PAGEREF _Toc419387408 \h  13
 

  HYPERLINK \l "_Toc419387409"  Table 7.  Recovery of Radioactivity in
CO2 Trap 2 from Group C.	  PAGEREF _Toc419387409 \h  14  

  HYPERLINK \l "_Toc419387410"  Table 7 (contd).  Recovery of
Radioactivity in CO2 Trap 2 from Group C.	  PAGEREF _Toc419387410 \h  15
 

  HYPERLINK \l "_Toc419387411"  Table 8.  Recovery of Radioactivity in
Exhaled VOC Trap 1 from Group C.	  PAGEREF _Toc419387411 \h  16  

  HYPERLINK \l "_Toc419387412"  a Samples from CM-04 were not analyzed.	
 PAGEREF _Toc419387412 \h  16  

  HYPERLINK \l "_Toc419387413"  * in LOD column indicates that sample
DPM were less than background DPM, and in LOQ column indicates that
sample DPM was less than 3 x background. Table 8 (contd).  Recovery of
Radioactivity in Exhaled VOC Trap 1 from Group C.	  PAGEREF
_Toc419387413 \h  16  

  HYPERLINK \l "_Toc419387414"  Table 8 (contd).  Recovery of
Radioactivity in Exhaled VOC Trap 1 from Group C.	  PAGEREF
_Toc419387414 \h  17  

  HYPERLINK \l "_Toc419387415"  a Samples from CM-04 were not analyzed.	
 PAGEREF _Toc419387415 \h  17  

  HYPERLINK \l "_Toc419387416"  Table 9.  Recovery of Radioactivity in
VOC Trap 2 from Group C.	  PAGEREF _Toc419387416 \h  18  

  HYPERLINK \l "_Toc419387417"  Table 9 (contd).  Recovery of
Radioactivity in VOC Trap 2 from Group C.	  PAGEREF _Toc419387417 \h  19
 

  HYPERLINK \l "_Toc419387418"  Table 10.  Recovery of Radioactivity in
Nose Only Tube Rinse from Group C.	  PAGEREF _Toc419387418 \h  20  

  HYPERLINK \l "_Toc419387419"  Table 11.  Recovery of Radioactivity in
Cage Rinse from Group C.	  PAGEREF _Toc419387419 \h  20  

  HYPERLINK \l "_Toc419387420"  Table 14.  Recovery of Radioactivity in
Carcass Digest from Group C.	  PAGEREF _Toc419387420 \h  21  

  HYPERLINK \l "_Toc419387421"  Table 15.  Total Recovery of
Radioactivity in Samples from Group C.	  PAGEREF _Toc419387421 \h  22  

  HYPERLINK \l "_Toc419387422"  Table 15 (contd).  Total Recovery of
Radioactivity in Samples from Group C.	  PAGEREF _Toc419387422 \h  23  

  HYPERLINK \l "_Toc419387423"  Table 15 (contd).  Total Recovery of
Radioactivity in Samples from Group C.	  PAGEREF _Toc419387423 \h  24  

  HYPERLINK \l "_Toc419387424"  Table 15 (contd).  Total Recovery of
Radioactivity in Samples from Group C.	  PAGEREF _Toc419387424 \h  25  

  HYPERLINK \l "_Toc419387425"  Table 15 (contd).  Total Recovery of
Radioactivity in Samples from Group C.	  PAGEREF _Toc419387425 \h  26  

Table 1.	  Male and Female Fischer 344 Rats Used on the Study	

Table 2.	  Exposure Conditions and Concentration of DIPE, Study A.	

Table 3.	  Exposure Conditions and Concentration of [2-14C]DIPE/DIPE,
Study B.	

Table 4.	  Exposure Conditions and Concentration of [2-14C]DIPE/13CDIPE,
Study C.	

Table 5.	  Concentration of DIPE in blood from male and female rats
exposed to 3600 ppm DIPE.	

Table 6.	  Concentration of Isopropanol in blood from male and female
rats exposed to 3600 ppm DIPE.	

Table 7.	  Concentration of Acetone in blood from male and female rats
exposed to 3600 ppm DIPE.	

Table 8.	  Pharmacokinetic Analysis of DIPE, Isopropanol and Acetone in
male and female rats exposed to 3600 ppm DIPE.	

Table 9.	  Total Recoverya of Radioactivity following Exposure to 3600
ppm [2-14C]DIPE/DIPE	

Table 10.	  Recovery of Radioactivity in Carcass following Exposure to
3600 ppm [2-14C]DIPE/DIPE (Group 2)	

Table 11.	  Recovery of Radioactivity in Excreta and Carcass following
Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 12.	  Recovery of Radioactivity in Urine following Exposure to
3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 13.	  Recovery of Radioactivity in Feces following Exposure to
3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 14.	  Recovery of Radioactivity in CO2 Trap 1  following exposure
to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 15.	  Recovery of Radioactivity in CO2 Trap 2 following exposure
to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 16.	  Recovery of Radioactivity in Exhaled VOC Trap 1 following
exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 17.	  Recovery of Radioactivity in Exhaled VOC Trap 2 following
Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 18.	  Cumulative Recovery of Radioactivity in Excreta and Carcass
following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 19.	  Recovery of Radioactivity in Tissues from Rat CM-02
following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	

Table 20.	  Normalized Recovery of Radioactivity in Exposure B and C
(Groups 2 and 3).	

Sample Naming and Abbreviations	

In the tables of raw data values in this appendix, the table headings
are derived from the conventions of sample naming used in the Debra(
system.  These are explained below.  Example calculations and formulae
are provided in Appendix G.	

Table 1.  Preparation of 14C DIPE Formulation (Feedstock) for Inhalation
Exposure	

14C DIPE for Study B	

Table 1 (contd).  Preparation of 14C DIPE Formulation (Feedstock) for
Inhalation Exposure	

13C/14C DIPE For Study C	

Table 2.  Recovery of Radioactivity in Samples from Group B.	

Table 3.  Total Recovery of Radioactivity in Samples from Group B.	

Table 4.  Recovery of Radioactivity in Urine from Group C.	

Table 4 (contd).  Recovery of Radioactivity in Urine from Group 2.	10

Table 5.  Recovery of Radioactivity in Feces from Group C.	11

Table 5 (contd).  Recovery of Radioactivity in Feces from Group C.	12

Table 6.  Recovery of Radioactivity in CO2 Trap 1 from Group C.	13

Table 6 (contd).  Recovery of Radioactivity in CO2 Trap 1 from Group C.
14

Table 7.  Recovery of Radioactivity in CO2 Trap 2 from Group C.	15

Table 7 (contd).  Recovery of Radioactivity in CO2 Trap 2 from Group C.
16

Table 8.  Recovery of Radioactivity in Exhaled VOC Trap 1 from Group C.
17

a Samples from CM-04 were not analyzed.	17

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. Table 8 (contd).  Recovery of Radioactivity in Exhaled VOC
Trap 1 from Group C.	17

a Samples from CM-04 were not analyzed.	18

Table 9.  Recovery of Radioactivity in VOC Trap 2 from Group C.	19

Table 9 (contd).  Recovery of Radioactivity in VOC Trap 2 from Group C.
20

Table 10.  Recovery of Radioactivity in Nose Only Tube Rinse from Group
C.	21

Table 11.  Recovery of Radioactivity in Cage Rinse from Group C.	21

Table 14.  Recovery of Radioactivity in Carcass Digest from Group C.	22

Table 15.  Total Recovery of Radioactivity in Samples from Group C.	23

Table 15 (contd).  Total Recovery of Radioactivity in Samples from Group
C.	24

Table 15 (contd).  Total Recovery of Radioactivity in Samples from Group
C.	25

Table 15 (contd).  Total Recovery of Radioactivity in Samples from Group
C.	26

Table 15 (contd).  Total Recovery of Radioactivity in Samples from Group
C.	27

Table 1.	  Male and Female Fischer 344 Rats Used on the Study	1716

Table 2.	  Exposure Conditions and Concentration of DIPE, Study A.	1817

Table 3.	  Exposure Conditions and Concentration of [2-14C]DIPE/DIPE,
Study B.	1918

Table 4.	  Exposure Conditions and Concentration of [2-14C]DIPE/13CDIPE,
Study C.	2019

Table 5.	  Concentration of DIPE in blood from male and female rats
exposed to 3600 ppm DIPE.	2120

Table 6.	  Concentration of Isopropanol in blood from male and female
rats exposed to 3600 ppm DIPE.	2221

Table 7.	  Concentration of Acetone in blood from male and female rats
exposed to 3600 ppm DIPE.	2322

Table 8.	  Pharmacokinetic Analysis of DIPE, Isopropanol and Acetone in
male and female rats exposed to 3600 ppm DIPE.	2423

Table 9.	  Total Recoverya of Radioactivity following Exposure to 3600
ppm [2-14C]DIPE/DIPE	2524

Table 10.	  Recovery of Radioactivity in Carcass following Exposure to
3600 ppm [2-14C]DIPE/DIPE (Group 2)	2625

Table 11.	  Recovery of Radioactivity in Excreta and Carcass following
Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	2726

Table 12.	  Recovery of Radioactivity in Urine following Exposure to
3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	2827

Table 13.	  Recovery of Radioactivity in Feces following Exposure to
3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	2928

Table 14.	  Recovery of Radioactivity in CO2 Trap 1  following exposure
to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3029

Table 15.	  Recovery of Radioactivity in CO2 Trap 2 following exposure
to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3130

Table 16.	  Recovery of Radioactivity in Exhaled VOC Trap 1 following
exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3231

Table 17.	  Recovery of Radioactivity in Exhaled VOC Trap 2 following
Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3332

Table 18.	  Cumulative Recovery of Radioactivity in Excreta and Carcass
following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3433

Table 19.	  Recovery of Radioactivity in Tissues from Rat CM-02
following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)	3534

 



List of Figures

Page

  TOC \h \z \t "Figure Title" \c "Figure"   HYPERLINK \l "_Toc351999983"
Figure 1.  Headspace GC-MS analysis of DIPE, acetone and isopropanol in
blood.	  PAGEREF _Toc351999983 \h  373635  

 HYPERLINK \l "_Toc351999985" Figure 2.  Concentration of DIPE in male
and female rat blood during and following exposure to 3600 ppm DIPE for
6 hours.	  PAGEREF _Toc351999985 \h  383736  

 HYPERLINK \l "_Toc351999986" Figure 3.  Concentration of Isopropanol in
male and female rat blood during and  following exposure to 3600 ppm
DIPE for 6 hours.	  PAGEREF _Toc351999986 \h  393837  

  HYPERLINK \l "_Toc351999987"  Figure 4.  Concentration of Acetone  in
male and female blood during and following exposure to 3600 ppm DIPE for
6 hours.	  PAGEREF _Toc351999987 \h  4139  

  HYPERLINK \l "_Toc351999988"  Figure 5.  Noncompartmental analysis of
DIPE in male (top) and female (bottom) rat blood during and following
exposure to 3600 ppm DIPE for 6 hours.	  PAGEREF _Toc351999988 \h  4240 


  HYPERLINK \l "_Toc351999989"  Figure 6.  Noncompartmental analysis of
isopropanol in male (top) and female (bottom) rat blood during and
following exposure to 3600 ppm DIPE for 6 hours.	  PAGEREF _Toc351999989
\h  4341  

  HYPERLINK \l "_Toc351999990"  Figure 7.  Noncompartmental analysis of
acetone in male (top) and female (bottom) rat blood during and following
exposure to 3600 ppm DIPE for 6 hours.	  PAGEREF _Toc351999990 \h  4442 


  HYPERLINK \l "_Toc351999991"  Figure 8.  Cumulative Excretion of
Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps.	  PAGEREF
_Toc351999991 \h  4543  

 

List of Appendices

Appendix A:	Approved Study Protocol, Amendments, and Deviations

Appendix B:	Test Chemical Analysis Report 

Appendix C:	Test Chemical Analysis Report:  2-14C Diisopropyl ether

		Test Chemical Analysis Report:  13C6-Diisopropyl ether

		Analysis of Reference Substances: Acetone and Isopropanol

Appendix D:  	Method Validation for Analysis of DIPE, Isopropanol and
Acetone

Appendix E:	Prestudy Inhalation Report

Appendix F:	Inhalation Reports

Appendix G	Equations Used inExample Calculations 

Appendix H 	Raw Data Tables for Radioactivity

Appendix I	Blood Sample Collection and Analysis for DIPE, Acetone and
IsopropanolRaw Data Tables for DIPE, Acetone and Isopropanol in Blood

Appendix J	Pharmacokinetic Analysis

1.0  	Introduction

The purpose of this pilot study was to develop and validate procedures
to be used to evaluate the adsorption, distribution, metabolism,
excretion and pharmacokinetics of diisopropyl ether (DIPE) in rats. 
DIPE is used as an oxygenate additive to gasoline.  

2.0  	Objectives and Protocol

The objectives of this pilot study were to: 

Study A

1) Collect blood from unexposed (control) male rats (n=10). 

2) Develop a gas chromatography (GC) method for the analysis of the
concentration of DIPE, isopropanol, and acetone in blood. 

3) Develop a nose-only exposure system for exposure of male and female
rats to DIPE, and conduct exposure of cannulated rats to unlabelled DIPE
(n=6; 3 backup unexposed).

4) Collect blood from rats exposed to unlabelled DIPE, and measure the
concentration of DIPE, isopropanol, and acetone in blood.

Study B

5) Conduct a nose-only exposure of male rats to 14C DIPE/DIPE (n=4; 1
backup unexposed).

6) Analyze the amount of 14C in whole body digests from rats exposed to
14C DIPE/DIPE.

Study C

7) Conduct a nose-only exposure of male rats to 14C DIPE/(U-13C6) DIPE
(n=4; 2 backup unexposed). 

8) Collect excreta from rats exposed to 14C DIPE/(U-13C6)  DIPE. 

9) Analyze 14C in whole-body digests, urine, feces, exhaled CO2, and
exhaled volatiles in rats exposed to 14C DIPE/(U-13C6)  DIPE.

10) Develop a method for analysis of metabolites in urine using HPLC and
NMR.

Copies of the approved protocol and protocol amendments for these
studies are included in Appendix A.  It should be noted that some of
these objectives listed above were involved method development
(development of a GC method for analysis, development of a nose only
inhalation exposure system) and were not conducted according to Good
Laboratory Practice.   

3.0  	Materials and Methods

3.1  	Test Substance

Name:  Diisopropyl ether (DIPE; CAS No. 108-20-3)

MOLECULAR FORMULA:  C6H14O

MOLECULAR WEIGHT:  102.18

STRUCTURE:  

 

3.1.1  	Nonradiolabeled diisopropyl ether

SOURCE OF NON-LABELED TEST SUBSTANCE:  The non-labeled DIPE was
purchased from Sigma-Aldrich, Milwaukee, WI.  A certificate of analysis
from the vendor indicated purity of 99.6% by GLC, with 6.6 PPM BHT

PRODUCT NUMBER:  398276

LOT NUMBER:  03658JC

The unlabeled test material was characterized at RTI by gas
chromatographic (GC) analysis for purity and stability, and for identify
by 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy and by
GC-mass spectroscopy.  Details of the analysis are included in Appendix
B.   

3.1.2  	(U-13C6)-labeled diisopropyl ether

SOURCE OF 13C-LABELED TEST SUBSTANCE:  (U-13C6) Substituted DIPE was
obtained from ISOTEC, Miamisburg, OH.  A certificate of analysis from
the vendor indicated purity of 95.9%.    

PRODUCT NUMBERS:  ISOTEC Number T83-03014

				ALDRICH Number 632384  

LOT NUMBER:  ST1187

The (U-13C6)-labeled diisopropyl ether was characterized at RTI by gas
chromatography-mass spectrometry analysis for identity, and by GC-FID
with a purity of 94.9%.  

3.1.2  	[2-14C]-labeled diisopropyl ether

Position of radiolabel:	[2-14C]-

Source:	American Radiolabeled Chemicals, Inc. St. Louis MO, prepared as
a custom synthesis

Specific Activity:	2.1 mCi/mmol 

Product No.:	ARC-3099

Lot No.:	070626

Identity:	The identity of [2-14C]-diisopropyl ether was confirmed by
chromatographic comparison with unlabeled DIPE using HPLC coupled with
radioactivity detection.

Purity:	The radiochemical purity of [2-14C]-diisopropyl ether was
determined chromatographically to be 97.23 %, using the HPLC system
described in Appendix C. 

The labeled test material was characterized at RTI by HPLC coupled with
radioactivity detection for purity and stability, and by HPLC coupled
with radioactivity detection and refractive index detection.  Details of
the analysis are included in Appendix C.   

3.2  	Reference Substances

Isopropanol.   2-propanol, product number 34863, lot number 05761JC was
obtained from Sigma-Aldrich.  The purity specified by the Vendor’s
certificate of analysis was 99.98%.  This material was assigned a
chemical receipt number of DPK-B-0005.  Identity of the material was
verified by 1H and 13C NMR spectroscopy, and by gas chromatography
coupled with mass spectrometry.  

Acetone, product number 34850, lot number 53250 was obtained from
Sigma-Aldrich.  Purity from the Vendor Certificate of Analysis was
99.9%. This material was assigned a chemical receipt number of
DPK-B-004.  Identity of the material was verified by 1H and 13C NMR
spectroscopy, and by gas chromatography coupled with mass spectrometry.

3.3  	Test System

Source:  Male Fischer 344 rats were purchased from Charles River
(Kingston, NY).  Animal weights at the time they were used in studies
are shown in Table 1.

Diet:  Animals were fed Certified Purina Rodent Chow #5002 and were
furnished tap water ad libitum.  The analysis of each feed batch for
nutrient levels and possible contaminants was performed by the supplier,
examined by the Study Director, and maintained in the study records. 
The feed was stored at approximately 60(70 (F, and the period of use
did not exceed six months from the milling date.  The source of the
water was the City of Durham, NC.  Approximately once a year, the City
of Durham provides analyses of the drinking water for potential
contaminants.  Documentation of these analyses were inspected by the
Study Director and maintained in the study records.  In addition,
samples of water were collected during before and after the study for
analysis of diisopropyl ethertertiary butanol, tertiary amyl methyl
ether, ethyl tertiary butyl ether, diisopropyl ether, and methyl
tertiary butyl ether.  The samples were sent to Kiff Analytical (Davis,
CA 95616) for analysis.   All of the analytes were below the reporting
limit for the method in the samples obtained before and after the study
(tertiary butanol 1 µg/L, tertiary amyl methyl ether 0.1 µg/L, ethyl
tertiary butyl ether 0.1 µg/L, diisopropyl ether 0.1 µg/L, and methyl
tertiary butyl ether 0.1 µg/L).

Identification:  Individual ear tags were used to uniquely identify
animals used.

Housing:  Rats were housed (maximum of three per cage) in polycarbonate
cages with stainless steel bar lids accommodating a water bottle until
they were used in an experiment.  Cage sizes are 19" x 10.5" x 8" high
(143 sq. in. floor space).  Contact bedding was Sani-Chips hardwood
chips (P. J. Murphy Forest Products Co.; Montville, NJ).  Cannulated
rats used in Study A were housed individually in cages with dimensions
of 9 ¼" x 10.5" x 8 ¼" high (approximately 76.3 sq. in. floor space)

Following exposure in Study C, 4 male rats were housed in individual
glass metabolism chambers for 7 days for collection of urine, feces,
exhaled CO2, and exhaled volatiles.  Two unexposed male rats were housed
in individual glass metabolism chambers for 2 days for collection of
urine, feces, exhaled CO2, and exhaled volatiles for determination of
radioactivity background.

Quarantine:  Rats were quarantined for a minimum of one week before use
on a study, with the exception of cannulated rats which were quarantined
for 1-2 days.  A veterinarian or qualified designee examined the animals
prior to their release from quarantine.  

Randomization:  The ear tag numbers of animals were assigned in
numerical order to sequential values using a series of computer
generated numbers as described in SOP DPK-HUS-001 Assignment of Animals
into Groups, using the procedure for Assignment of Animals within a
Single Group or Multiple Groups without Regard to Weight Mean and Range.
 Four groups were prepared:  Study A (n=9 for males and females), Study
B (n=4), Study C (n=4).  

Environmental:  Temperature and relative humidity in RTI animal rooms
were continuously monitored, controlled, and recorded using an automated
system (Siebe/Barber-Colman Network 8000 System with Revision 4.4.1 for
Signal( software [Siebe Environmental Controls (SEC)/Barber-Colman
Company; Loves Park, IL]).  The target environmental ranges were
64(79 (F (18 (C - 26 (C) for temperature and 30(70% relative
humidity, with a 12-h light cycle per day.

Euthanasia:  At the end of the in-life phase, the rats were euthanized
by overexposure to carbon dioxide.

3.4  	Test Chemical Preparation and Analysis

For inhalation exposure to unlabeled DIPE (Study A), an appropriate
amount of unlabeled DIPE was prepared for generation of the exposure
atmosphere, calculated based on the exposure concentration, the duration
of exposure, the number of animals, and the flow rate of air through the
exposure tower.  

For inhalation exposure to [2-14C]DIPE/DIPE (Study B), 14C DIPE was
added to an appropriate amount of unlabeled DIPE for generation of the
exposure atmosphere.   The amount of labeled and unlabeled DIPE required
was calculated based on the exposure concentration, the duration of
exposure, the number of animals, and the flow rate of air through the
exposure tower.  

For inhalation exposure to [2-14C]DIPE/(U-13C6)DIPE (Study C), 14C DIPE
was added to an appropriate amount of (U-13C6)DIPE for generation of the
exposure atmosphere.   The amount of labeled and (U-13C6)DIPE required
was calculated based on the exposure concentration, the duration of
exposure, the number of animals, and the flow rate of air through the
exposure tower.  

For inhalation exposure to [2-14C]DIPE/DIPE, [2-14C]DIPE was weighed
into a tared flask with a Teflon faced screw cap.  The weight of the
labeled chemical added was recorded.   Unlabeled DIPE was added, and the
weight added was recorded.  The nominal specific activity of the DIPE
mixture was then calculated.  This was verified by weighing an aliquot
into a sealed flask, recording the weight added, and adding solvent, and
recording the weight added.  Aliquots of the solution of DIPE were
placed in scintillation vials, and the weight added was recorded.  The
amount of solution added was calculated based on the density of the
solvent.  Ultima Gold™ scintillation cocktail (Perkin Elmer) was added
to the scintillation vials, and the amount of radioactivity added was
determined by liquid scintillation spectroscopy (LSS).  The specific
activity of the labeled DIPE was then calculated from the data obtained.

A procedure analogous to that described above was followed for the
preparation of [2-14C]DIPE/(U-13C6)DIPE.

The exposure atmosphere concentration was monitored using a calibrated
Miran IR detector.   The concentration of DIPE was monitored
continuously at the inlet to the tower, and at the outlet.  The
stability of DIPE under the conditions of administration was monitored
by sampling the inlet of the exposure tower during the exposure and at
the end of the exposure (Appendix F).  Samples of the exposure
atmosphere were collected using a 1ml syringe, and bubbled through water
for analysis by HPLC, and through methanol for analysis by GC-MS.  

3.5  	Inhalation Exposure

A single nose-only inhalation exposure to [2-14C]DIPE/DIPE was conducted
with a total of 9 8 male and 9 8 female rats for Study A on September
27, 2007.  A single nose-only inhalation exposure to [2-14C]DIPE/DIPE
was conducted with a total of 4 male rats for Study B on October 3,
2007.   A single nose-only inhalation exposure to
[2-14C]DIPE/(U-13C6)DIPE was conducted with a total of 4 male rats for
Study C on October 4, 2007. For each study, the DIPE preparation was
drawn into a clean syringe.  The generation system consisted of a
syringe containing DIPE with a syringe pump to deliver the chemical to
the air supply of the exposure chamber.  The DIPE exposure atmosphere
was generated by pumping liquid DIPE into the air stream flowing into a
Cannon nose-only exposure system.  The syringe pump and clean air flow
rate were set such that a target concentration of 3600 ppm was achieved.
 The exposure air flow rate delivered to each animal was at least 1.5
times the animal minute ventilation rate.  The air supply was controlled
with an electronic mass flow meter to maintain a total air flow of at
least 12 air changes per hour.  The generation and delivery system were
placed in a chemical hood to contain any DIPE that might leak from the
system.

The exposure system (see Appendix E and Appendix F) consisted of a
Cannon flow-past nose-only exposure system containing 52 exposure ports.
 This chamber is a dynamic non-rebreathing system that allows for the
simultaneous exposure of up to 51 animals.  The chamber is cylindrical
in shape, and is constructed in stainless steel.  Unused ports were
plugged with solid metal rods to reduce consumption of the exposure
material.  The Cannon nose-only chamber operated on a push-pull basis. 
The sampling lines and main exposure atmosphere delivery lines were
Teflon.   The incoming air for the exposure system was filtered to
eliminate the possibility of contamination in the air supply.  To the
extent possible, tThe air supply temperature and relative humidity were
maintained between 64 to 79 degrees Fahrenheit and 30 to 70 %,
respectively.  The chamber exhaust flow was adjusted to maintain a
slight negative pressure during the exposure to prevent DIPE from
entering the laboratory area. The chamber exhaust was filtered through a
disposable charcoal filter and disposed at the end of the exposure.  
Closed nose-only tubes were used to hold the test animals during
inhalation exposures.  The inhalation system was strategically placed in
a chemical hood to prevent any DIPE from entering the laboratory.

3.5.1 Exposure Analysis

Prior to the inhalation exposure of rats, the performance of the
inhalation system was verified to ensure that the test atmosphere could
be generated on the nose only tower to achieve the test concentration
over the duration of the exposure (≤ 10% difference between actual and
target concentration), and that the port to port variability was within
accepted limits (≤ 10% difference in measurement taken at multiple
locations on the tower). A report describing the preexposure
characterization of the inhalation system is attached to this report as
Appendix E, and a report reports characterizing the exposures of rats is
are attached as Appendix F.  Note that during the sampling of air at the
ports on the inhalation exposure system to establish port to port
variability, the air sampled was diluted with additional makeup air
added to enable more rapid sampling.  The sampling was conducted to
demonstrate port to port variability, and with the same proportion of
makeup air added over the course of the exposure, the determination of
variability is valid, even though the mean concentration sampled at the
port is less than the 3600 ppm concentration determined at the inlet.

3.6  	Collection of Samples

3.6.1	Blood Sample Collection

For Study A, blood samples were collected by jugular vein cannula prior
to dosing from each rat (time = 0), and from three rats of each sex, at
approximately 5 min, 10 min, 15 min, 30 min, and at approximately 1, 2,
4 and 6 hr after the exposure initiation.  At the end of the 6 hr
exposure, all rats were removed from the inhalation exposure tower, and
placed in cages.  Blood was drawn from three rats at approximately 375,
390, 420, 440, 480, 600, 960, and 1440 min after the beginning of the
exposure (at approximately 15, 30, 60, 80 min, and 2 hr, 4 hr, 10 hr,
and 18 hr after the end of the exposure).  To facilitate the withdrawal
of blood samples, animals were stagger-started on the exposure tower. At
each time point approximately 100 L of blood was withdrawn using a
heparinized syringe.  

Blood samples were drawn from the jugular vein cannula into a
heparinized 1 ml syringe, and the sample was immediately placed in a
preweighed headspace vial.  The amount of blood was approximately 100
µl.  The vial was immediately crimped and weighed, and the weight of
the blood aliquot was determined.  After the last sample has been
collected from each animal, the rats were euthanized by exposure to CO2.
 The blood samples were maintained on ice, until placed in the headspace
autosampler for analysis.  All blood samples were analyzed by GC-MS
within 24 hours of collection.  

Blood samples from unexposed rats were used for method development. 
Blood samples were collected by cardiac puncture, under CO2 anesthesia,
and the rats were euthanized.

3.76.12	Excreta

In Study C, 4 rats (CM-01, CM-02, CM-03, and CM-04) were placed in
all-glass metabolism cages for the separate collection of urine, feces,
exhaled volatiles, and exhaled CO2.  Urine was collected over dry ice at
0(8, 8(24, 24(48, 48(72, 72(96, 96(120, 120(144, and 144(168 hours after
termination of exposure.  Feces were collected over dry ice at 0(24,
24(48, 48(72, 72(96, 96(120, 120(144, and 144(168 hours after
termination of exposure.  Exhaled volatile organics were collected on a
series of two charcoal traps (Product Number 226-16, SKC Sorbent Tube,
Anasorb CSC, Coconut Charcoal, 10 X 110 mm size, 2-section, 200/800 mg
sorbent, SKC Inc, Eighty Four, PA) at 0(1, 1(3, 3(6, 6(24, 24(48, 48(72,
72(96, 96(120, 120(144, and 144(168 hours after termination of exposure.
  Expired 14CO2 was collected in 1.0 N KOH at 0(1, 1(3, 3(6, 6(24,
24(48, 48(72, 72(96, 96(120, 120(144, and 144(168 hours after
termination of exposure.   At the end of excreta collection, the cages
were rinsed with water and with ethanol, and combined.   The rinses were
analyzed for total radioactivity.  The weight of urine and/or feces
collected for each sample interval was measured.  Urine and feces were
analyzed for total radioactivity.  Excreta not assayed within a day of
collection were stored at approximately -20 (C in the dark.

Two unexposed rats were housed in all-glass metabolism cages for 48
hours, as described above, for the collection of urine, feces, and
exhaled volatiles, and exhaled CO2.  The samples collected were used to
supply background samples for the analysis of radioactivity.

3.6.23	Carcass 

For Study B, the amount of 14C retained was determined by placing each
rat in the nose-only restraint tube in a Tedlar gas bag.  The bag was
sealed, and CO2 was pumped into the bag to euthanize the rat.  The gas
from the gas bag was then forced through a charcoal filter trap, to
determine the amount of exhaled 14C, and the carcass was digested with
2N ethanolic NaOH.  After sample digestion, the amount of radioactivity
in the carcass was determined by LSS.  Any feces in the nose-only
restraint tube were collected and the amount of radioactivity in the
feces sample was determined by LSS.  The nose-only tube was rinsed with
water, and the amount of 14C contained in the rinse was determined by
LSS.  

For Studies B and C, the carcasses were digested with 2N ethanolic NaOH.
 After sample digestion, the amount of radioactivity in the carcass was
determined by LSS.  

3.6.24	Tissues

For Study C, tissues were obtained following sacrifice from a single rat
(CM-02):

 femur					cecum + large intestine + rectum

skin (hair shaved)			small intestine

subcutaneous fat			liver

abdominal fat				muscle (gastrocnemius)

brain					heart

testes (epididymis removed)		kidneys

stomach contents 			small intestine contents

stomach				large intestine + cecum contents 

lungs					spleen 	

residual carcass

The harvested tissues were weighed and analyzed for radiochemical (14C)
content by LSS.  The remaining carcass of the animal from which the
tissues listed above have been taken will bewas analyzed for total
radioactivity.  Tissues will bewere prepared as described in section
83.68.23 below.

3.8  7  	Analysis of Blood Samples for DIPE, Isopropanol, and Acetone

A GC-MS method was developed for quantitating DIPE, isopropanol and
acetone using blood from control male Fischer 344 rats.  The methods
development involved the generation of a standard curve for analysis of
DIPE, isopropanol and acetone in the headspace of airtight vials
containing a known volume of control blood and a known concentration of
each analyte.  The stability of DIPE, isopropanol and acetone was
evaluated under storage conditions that were used in this study during
this method development.  This included analysis of DIPE, isopropanol
and acetone immediately after spiking in control blood, after storage at
room temperature (8 hr), or at approximately 4oC (24 16 hr).  The
concentration of DIPE, isopropanol and acetone in the headspace of vials
containing a known volume of blood from rats administered DIPE by
inhalation was determined by comparison to the standard curve.  A
detailed description of the analytical method is contained in Appendix
C.  

The method was applied to the analysis of samples obtained from jugular
vein cannulated rats exposed to DIPE by inhalation.  Blood samples were
obtained from cannulas (or in the cases where samples could not be
obtained via the cannula, from the tail vein) as described in section
3.6.1.  Samples were transferred immediately to headspace vials, crimp
sealed, and analyzed as described in Appendix C.  Vials and caps were
weighed prior to addition of blood, and after addition of blood, and the
weight of blood added was calculated.  Internal standard solution (10
µL) containing MTBE (50 µg/mL) and 1-propanol (500 µg/mL) was added
using a 10-µL microsyringe.  After analysis by headspace GC-MS, the
concentration of each analyte was corrected for the weight of blood
collected.  The method is described in detail in Appendix C.

3.8  	Analysis of Samples for Total Radioactivity

Ultima Gold™ scintillation cocktail was used in all determinations of
radiochemical content.  Radioactivity was determined using a Packard
1900CA Liquid Scintillation Counter.  Weights of samples collected were
recorded, and aliquots were prepared by weight for scintillation
counting. 

3.8.1	Excreta

Duplicate aliquots of urine (approximately 0.05 g) were analyzed
directly (without solubilization or bleaching) for radiochemical
content.  Duplicate aliquots of urine were weighed into scintillation
vials containing scintillation cocktail.  Feces were homogenized with an
approximately equal mass of water.  The weight of the feces homogenate
was determined, and duplicate homogenate aliquots were weighed into
scintillation vials.  After solubilization of the homogenate aliquots
with Soluene-350™ (about 2 ml per sample), scintillation cocktail was
added to the vials, and the samples were analyzed for total
radioactivity by LSS.  Samples were bleached (by adding approximately
125 µl of 70% perchloric acid, and then approximately 0.3 ml of 30%
H2O2) prior to addition of scintillation cocktail.  Control samples of
urine and feces were collected from unexposed animals and analyzed as
described above to determine background counts.

3.8.2	Tissues and Carcass

Carcasses were analyzed for total radioactivity following solubilization
in 2N ethanolic NaOH.  Duplicate samples of the solubilized carcass were
analyzed.  Tissues were analyzed for total radioactivity following
solubilization in Soluene-350™ (about 2 mL per tissue sample).   
Liver was homogenized, and duplicate aliquots of the homogenate
solubilized.  Other tissues were solubilized in their entirety or after
being divided into multiple pieces.  Solubilized tissue samples were
bleached (by adding approximately 125 µl of 70% perchloric acid, and
then approximately 0.3 ml of 30% H2O2) prior to addition of
scintillation cocktail and analysis by LSS. 

Control samples of carcass and tissues were collected from unexposed
animals and analyzed as described above to determine background counts.

3.8.3  Exhaled Breath Traps

Aliquots of 1.0 N KOH from the exhaled breath trap for CO2 were analyzed
by LSS after addition of scintillation cocktail.  

3.8.4  Exhaled Volatiles Traps

Each charcoal trap was extracted by elution with dimethylformamide (DMF)
to determine absorbed radioactivity.  For a single extraction, charcoal
was transferred to a centrifuge tube and weighed.  DMF (8.0 ml for
samples of VOC Trap 1 from 0 – 24 h, and 4.0 ml for samples collected
following 24 h) was added, and the sample weighed.  After vortexing for
approximately 30 seconds, the samples were centrifuged, and the
supernatant was removed.  The DMF was removed following centrifugation
and radioactivity was determined in duplicate aliquots of the DMF
extract by LSS.     

3.9  	Data Collection and Reporting

Study data was collected and reported in the Debra™ system version
5.5.10.7275.  This includes data for pot weights, sample weights,
homogenate weights and aliquot weights, and scintillation counting data.
 Calculations of sample data are described in Appendix G, and were
reported with the Debra™ system.  Individual values for sample weights
and radioactivity determinations are presented in Appendix H.  Data for
radioactivity where the sample aliquot dpm values were below the
background for the sample were considered to be less than the limit of
detection, and are reported as 0 dpm per aliquot.  Data for all samples
that were above the limit of detection are reported, and included in
calculations.  However, where the sample aliquot dpm values were less
than three times the background for the sample, the sample has been
flagged with an asterisk in the Summary Tables and appendix tables.    

4.0  	Results

4.1  	Analysis of Radiolabeled Test Chemical Identity and Purity

Information on the identity, purity, and stability of the test chemical
is included in Appendix B.  Prior to study initiation, the test chemical
purity was determined by GC to be 99.38 ( 0.16 %.  Following completion
of the study, test chemical purity was determined to be 99.71 63 ( 0.01
006 %.  The radiochemical purity of 2-14C DIPE specified by the vendor
was 96.83 % by HPLC, and was verified by HPLC at RTI prior to the
inhalation exposure of rats as 9897.37 23 ( 0.2404% (Appendix C).  A
sample of the exposure atmosphere was taken from the tower inlet to
measure purity of the radiolabeled test chemical during the exposure. 
The purity of the radiolabeled material was determined to be 94.6 ( 2.4
%.  The purity of the (U-13C6) DIPE specified by the vendor was 95.9 %
and was verified by NMR spectrocscopyspectroscopy, and by GC as 95.17 ±
0.03 %.  Analysis of the reference substances acetone and isopropanol is
reported in Appendix DC.    

4.2  	Test Chemical Formulation

For Study A, unlabeled DIPE was used for generating the exposure
atmosphere.  For Study B, the test chemical was prepared by mixing
unlabeled DIPE with 2-14C labeled DIPE, and used without further
dilution.  The specific activity of the formulation is reported in Table
23, and was measured as 0.4503 µCi/mg.   For Study C, the test chemical
was prepared by mixing (U-13C6) DIPE with 2-14C labeled DIPE, and used
without further dilution.  The specific activity of the formulation is
reported in Table 34, and was measured as 0.4241 µCi/mg.ch

4.3  	Inhalation exposure

The body weights of the animals used during the course of Studies A, B
and C are shown in Table 1.  The exposure concentration data for each
six-hour exposure of rats to a target concentration of 3600 ppm DIPE is
shown in Table 2, 3, and 4.  The details of the inhalation exposure
system are described in Appendix E, Inhalation Summary Report for Setup
and Evaluation of Inhalation System at RTI International and the details
of the actual exposure are reported in Appendix F, Inhalation Summary
Reports: DIPE, 14C-DIPE/DIPE and 14C-DIPE/13C-DIPE Nose-Only Inhalation
Exposure at RTI International.  The actual exposure concentration was
3643 ( 177 ppm for Study A (Table 2), 3529 ( 40 ppm for Study B (Table
3), 3334 ( 99 ppm for Study C  (Table 4).   The exposure duration for
Study C was less than 6 hours, with the limited supply of 13C DIPE
providing an exposure duration of 5 hours and 40 minutes.  Analyses of
samples of the exposure atmosphere are reported in Appendix F, Analysis
of Exposure Atmospheres: Diisopropyl Ether.   GC-MS analysis of samples
of the exposure atmosphere sampled during Studies A, B and C confirmed
the presence of DIPE or 13C6-DIPE in the exposure atmosphere near the
beginning and end of the exposures, verifying the stability of DIPE in
the inhalation system. With the exception of one sample that showed a
small peak containing acetonitrile, that is thoguththought to have
arisen from contamination of a sampling syringe, there were no
significant impurity peaks suggesting that the DIPE is stable in the
inhalation system.  Radioactivity from air samples collected during the
course of the inhalation exposures for Studies B and C chromatographed
with the expected retention time of DIPE on HPLC.  However, the levels
of radioactivity recovered were insufficient to reliably establish
purity.   

      

4.4  	DIPE, Acetone and Isopropanol in Blood During and  Following
Exposure

DIPE, isopropanol and acetone were determined by headspace GC-MS
analysis in blood samples obtained from jugular vein cannulated male and
female rats (Study A, Group 1, rats AM-01 – AM-08, AF-01 – AF-08). 
The concentrations determined are presented in Tables 5 - 7 9 and in
Figures 1 - 34.  DIPE was less than the limit of quantitation (LOQ) in
preexposure samples.  DIPE accumulated rapidly during the 6 hours of
exposure, and rapidly declined after the exposure.  There was little
difference in blood levels at peak concentration between males and
females.  All samples were below LOQ by 16 hr. In the male rats, blood
concentrations of isopropanol was were below LOQ in preexposure samples,
all three samples collected at 5 min, and in one of the three collected
at 10 min.  The concentration of isopropanol rose steadily during the
exposure, and then declined gradually.  In male rats, blood
concentrations of isopropanol reached peak concentrations at
approximately twice those of female rats.  All samples were below LOQ by
16 hr.  In the female rats, isopropanol blood concentrations was were
below LOQ in preexposure samples, and all samples collected at 5 10, and
15 min.  The concentration of isopropanol rose steadily during the
exposure, and then declined gradually.  In male rats, blood
concentrations of isopropanol peaked at approximately twice those of
female rats.  All samples were below LOQ by 16 hr.  In male and female
rats, acetone was above LOQ in 5 of the 6 preexposure samples.  Acetone
levels in both male and female rats rose steadily during the exposure,
and in males continued to rise following exposure until 8 hr following
the initiation of exposure.  In both males and females, the acetone
levels were approximately the same between 6 and 8 hours following the
exposure, and then declined rapidly reaching preexposure levels by 16
hrs in females and 24 hrs in males.  The concentration achieved in males
exceeded the range of the calibration curve, and for some samples
obtained between 6 4 hours and 10 hours, concentrations are estimated by
linear extrapolation of the calibration curve.  The peak concentrations
of acetone achieved in male rats were approximately 50% higher than
those in female rats.   Male rats reached preexposure levels by 24
hours.  

Noncompartmental pharmacokinetic analysis was conducted using the mean
concentration of DIPE, isopropanol or acetone rather than individual
values.  With the alternating sampling of the animals during and
following exposure, the use of mean values with all of the data points
provides the best pharmacokinetic analysis.   With noncompartmental
analysis, the elimination rate constant and half life are determined
from the rate of decline of blood concentration following the end of the
exposure.  Semi-log plots of concentration vs. time for DIPE in blood
are shown in Figure 45.   Pharmacokinetic analysis of DIPE indicated a
half life of 0.92 h in male rats, and 0.76 h in female rats (Table 8). 
Isopropanol had an apparent half life of 1.16 and 1.23 h in male and
female rats, respectively (Table 8 and Figure 56).  Acetone had an
apparent half life of 2.31 and 2.32 h in male and female rats,
respectively (Table 8 and Figure 67).  Acetone achieved the highest
levels in blood (Cmax values of 319 and 211 µg /mL in male and female
rats, respectively), compared with DIPE (Cmax values of 56 and 66 µg
/mL in male and female rats, respectively), and isopropanol (Cmax values
of 66 and 36 µg /mL in male and female rats, respectively). The peak
concentrations of acetone achieved in male rats were approximately 50%
higher than those in female rats, and for isopropanol the peak
concentrations in males were almost twice those in females.    Tmax
values for DIPE were at 4 h in male rats and 6 h in female rats.  The
Tmax values for acetone and isopropanol occurred at between 6 and 6.5 h,
suggesting that the metabolism of DIPE to isopropanol and acetone occurs
rapidelyrapidly.   Acetone achieved the highest area under the curve
(AUCall values of 3208 and 1735 µg·hr/mL in male and female rats,
respectively) compared with isopropanol (AUCall values of 339 and 156
µg·hr/mL in male and female rats, respectively) and DIPE (AUCall
values of 312 and 363 µg·hr/mL in male and female rats, respectively).

4.5  	Radioactivity Retained Following Exposure

Four rats were euthanized immediately following inhalation exposure to
[2-14C]DIPE/DIPE (Study B, Group 1, rats BM-01, BM-02, BM-03, and
BM-04).  The amount of radioactivity retained in the carcass was
determined by solubilization followed by scintillation counting.  The
total radioactivity retained and the estimated dose in mg/kg are
presented in Table 9.  The amount of radioactivity retained in Group B
ranged from approximately 33 to 34 35 µCi.  The estimated dose was 373
( 8 mg/kg.   This estimate of dose included radioactivity recovered in
carcass, a VOC trap that was used to trap any exhaled volatiles while
the rat was in the transfer bag, the nose only tube wash, and feces
recovered from the nose only tube.   The vast majority (98.6%) of the
radioactivity was recovered in the carcass (Table 10).  

4.6  	Excretion of Radioactivity

Four rats were placed in metabolism cages for collection of urine and
feces and exhaled breath immediately following the inhalation exposure
to [2-14C]DIPE/DIPE (Study C, Group 3, Rats CM-01, CM-02, CM-03, and
CM-04).  Transfer of the rats from the inhalation tower to the
metabolism cage was conducted with the rat retained in the nose-only
tube contained within a polyethylene bag.  Following transfer of the rat
to the metabolism cage, radioactivity retained in the bag was recovered
by washing with water.  The nose-only tube was washed and any feces were
collected for digestion and scintillation counting.  The rats were
maintained in the metabolism cages for 7 days following the end of the
exposure.  The exhaled breath traps from one rat were not analyzed, but
were saved to provide an opportunity for analysis at a later date, and
are not included in calculations of recovery.  The total recovery of
radioactivity from all of the samples collected from rats in Group 3,
Study C is presented in Table 9, and ranged from approximately 25 to 28
µCi (with the exception of rat CM-04,where exhaled breath traps were
saved for possible future analysis).  The estimated dose was 299 318 ( 7
8 mg/kg (excluding CM-04, Table 9).   

The amount of radioactivity in urine, feces, exhaled VOCs, and CO2
expressed as a percentage of the total radioactivity recovered is
presented in Table 11.  Exhalation of volatile material was the primary
route of elimination, with 71% of the recovered radioactivity trapped in
the Exhaled VOC Traps. Exhaled 14CO2 accounted for approximately 20.2 %
of the recovered radioactivity.  Approximately 5 % and 1% were excreted
in urine and feces, respectively.  

Radioactivity in urine was excreted primarily in the first 24 hours
(Table 12), with 3% and 1.5% at 12 8 and 24 hours, respectively.  Less
than or equal to 0.2 % or less of the radioactivity was recovered in
urine at 48, 72, 96, 120, 144, and 168 hours.  In feces (Table 13),
approximately 0.6 % of the recovered activity was found in the 0-24 h
samples, which contained the largest amount of fecal radioactivity.   

Radioactivity in the first CO2 trap was excreted primarily in the first
24 hours (Table 14).  Little radioactivity was recovered in the second
CO2 trap (Table 15).  Many of the samples collected contained levels of
radioactivity that were below 3 times background.

The majority of the radioactivity retained on the charcoal traps for
exhaled volatiles was retained on the first charcoal trap of two in
series in the first 24 hours (Table 16).  Each of the Exhaled VOC Trap 1
samples collected between 0 and 24 hours contained a substantial portion
of the dose.  Very little of the dose was trapped in the VOC Trap 2
samples (Table 17), with the exception of the 6-24 h samples for rats
CM-01 and CM-02.  

The cumulative excretion of radioactivity (Table 18) shows that
approximately 94% of the radioactivity was recovered within 24 h
following exposure, and 95% of the activity was recovered by 48 hours
following exposure.  

Tissue recovery was evaluated for one rat at 7 days following exposure
(Table 19).  Liver contained approximately 0.12 % of the recovered
radioactivity.  All other tissues collected contained lower percentages
of the dose.

5.0  	Discussion

The objectives of the study were accomplished.  An inhalation exposure
system was developed, and used to conduct the exposures to 3600 ppm
DIPE.   A headspace GC-MS method for analysis of DIPE, isopropanol, and
acetone was developed, and applied to samples from male and female rats
exposed to DIPE.  The disposition of 14C DIPE was evaluated in male
rats, and determined immediately after exposure, and up to 7 days
following exposure.  The extent of excretion of metabolites in urine was
less than 5% of the dose, so the objective of determining the identity
of metabolites in urine was modified.   

 Comparison of the exposure of rats to 3600 ppm [2-14C]DIPE/DIPE
euthanized immediately following exposure (372 ( 8 mg/kg) with that of
rats euthanized following 7 days of collection of excreta and exhaled
breath (299 318 ( 7 8 mg/kg) yielded values that were very similar. 
Normalization of these values based on the actual exposure
concentrations and the duration of exposure (Table 20) reduced the
extent of the difference, with 0.176 mg/kg/ppm.hr immediately after
exposure, and 0.168 mg/kg/ppm.hr at 7 days, indicating a recovery of
approximately 95.6%.  This suggested that there were no significant
losses of radioactivity from the various sample types during processing
of radioactivity.

Radioactivity was rapidly excreted by exhalation as volatile components
(71% of the recovered radioactivity) and as 14CO2 (2520.2% of the
recovered radioactivity).  The cumulative excretion of radioactivity was
94% and 95% within 24 and 48 hours, respectively, of the end of the
exposure.  At seven days, only 02.6% was recovered in the carcass.  

DIPE in blood was readily detected during and after exposure.  DIPE
levels fell rapidly following the end of the exposure, reaching the
limit of quantitation by 10 hours after initiation of exposure.  
Acetone and isopropanol were detected in blood, increasing with the
duration of exposure and decreasing following the end of the exposure. 
The acetone levels were substantially higher than those of DIPE and
isopropanol.  The conversion of DIPE to isopropanol and acetone is
consistent with the high recovery of radioactivity in the exhaled breath
volatiles and as 14CO2.  

6.0  	References

Cannon, W. C., Blanton, E. and McDonald, K. E. (1983). The flow-past
chamber: an improved nose-only exposure system for rodents. Am. Ind.
Hyg. Assoc. J. 44, 923-928.

Dalbey, W. and Feuston, M. (1996). Subchronic and developmental toxicity
studies of vaporized diisopropyl ether in rats.  J Toxicol Environ
Health 49, 29-43. 

Grubbs FE (1969). Procedure for detecting outlying observations in
samples. Technometrics, 11:1–21.

National Research Council (1996).  Guide for the Care and Use of
Laboratory Animals.  National Academy Press: Washington, DC.

US Food and Drug Administration (2001).  Guidance for Industry:
Bioanalytical Method Validation. 

7.0  	RECORDS and Reports

The following will be maintained in the record:

Protocol and any amendments

Animal receipt records

Quarantine records

Temperature and humidity records for the treatment rooms

Animal research facility room logs

Feed and water analysis for contaminants

Randomization records

Test chemical receipt, storage, and use records

Balance calibration log references

Correspondences

All other raw data and documentation

Upon acceptance of the audited draft report by the Sponsor, a final
report will be issued.  

8.0  	Storage of Records and Biological Samples

A copy of the final report and the records for this study, including all
raw data, will be retained in the RTI Archives, under the responsibility
of the RTI Quality Assurance Unit, for the length of time specified in
the appropriate regulations.

Biological specimens that remain stable for reanalysis and samples of
nonradiolabeled and radiolabeled DIPE  will be stored at RTI in a
secured area by the RTI project number for up to two 10 years after the
date of submission of the final report.

The Sponsor will be notified in writing when the RTI retention time has
expired.

9.0  	REGULATORY COMPLIANCE

These studies were performed in compliance with the EPA Good Laboratory
Practices (GLP) Standards for Inhalation Exposure Health Effects
Testing, 40 CFR part 79, subpart F § 79.60.  Deviations from the
approved protocol are documented in Appendix A. 

10.0  	STUDY PARTICIPANTS

RTI International

Study Director: 	Timothy R. Fennell, Ph.D.

Veterinarian: 	J.S. Scott-Emuakpor, D.V.M.

Animal Facility Supervisor: 	

Laboratory Staff:  	N. F. Gaudette, BS

	Y. Hong, BS

	R. W. Snyder, MS

	M. P. Gower

Secretary: 	K. G. Ancheta

	

Quality Assurance Reviewer:  K. Collier

	C. Ingalls

	C. Keller

	B. Rauscher

CIIT Centers for Health Research

Principal Investigator:: 	R Arden James.

Laboratory Staff:  	K. Roberts

	

Quality Assurance Reviewer:  P. O’Brien Pommerleau	

	A. Matrone

Table   SEQ Table \* ARABIC  1 .	  Male and Female Fischer 344 Rats
Used on the Study

Group	Subject	Species	Strain	Gender	Body Wta

Group 1 Study A	AM-01	Rat	Fischer 344	Male	185.10 g

Group 1 Study A	AM-02	Rat	Fischer 344	Male	172.51 g

Group 1 Study A	AM -03	Rat	Fischer 344	Male	191.92 g

Group 1 Study A	AM-04	Rat	Fischer 344	Male	185.81 g

Group 1 Study A	AM-05	Rat	Fischer 344	Male	163.70 g

Group 1 Study A	AM-06	Rat	Fischer 344	Male	173.98 g

Group 1 Study A	AM -07	Rat	Fischer 344	Male	164.56 g

Group 1 Study A	AM-08	Rat	Fischer 344	Male	177.08 g

Group 1 Study A	AF-01	Rat	Fischer 344	Female	117.23 g

Group 1 Study A	AF-02	Rat	Fischer 344	Female	122.97 g

Group 1 Study A	AF-03	Rat	Fischer 344	Female	112.56 g

Group 1 Study A	AF-04	Rat	Fischer 344	Female	114.36 g

Group 1 Study A	AF-05	Rat	Fischer 344	Female	118.86 g

Group 1 Study A	AF-06	Rat	Fischer 344	Female	119.86 g

Group 1 Study A	AF-07	Rat	Fischer 344	Female	116.93 g

Group 1 Study A	AF-08	Rat	Fischer 344	Female	112.15 g

Group 2 Study B	BM-01	Rat	Fischer 344	Male	200.58 g

Group 2 Study B	BM-02	Rat	Fischer 344	Male	203.03 g

Group 2 Study B	BM-03	Rat	Fischer 344	Male	202.66 g

Group 2 Study B	BM-04	Rat	Fischer 344	Male	197.58 g

Group 3 Study C 	CM-01	Rat	Fischer 344	Male	188.27 g

Group 3 Study C 	CM-02	Rat	Fischer 344	Male	187.41 g

Group 3 Study C 	CM-03	Rat	Fischer 344	Male	208.47 g

Group 3 Study C 	CM-04	Rat	Fischer 344	Male	190.91 g

Group 4 Study C BKGb	CB-01

Fischer 344	Male	197.34 g

Group 4 Study C BKGb	CB-02

Fischer 344	Male	200.99 g



aBody weight on the day of exposure

bAnimals used in Group 3 and Group 4 were not exposed to
[2-14C]DIPE/DIPE, and provided samples for determination of background
only.

Table   SEQ Table \* ARABIC  2 .	  Exposure Conditions and
Concentration of DIPE, Study A.

	Target  (ppm) 

Number of Open Ports	3600

17





ACC - Inlet	Mean	3643

(ppm)	Std Dev	177

	No. of Data Points	14





ACC - Exhaust	Mean	3470

(ppm)	Std Dev	48

	No. of Data Points	14





Exposure	Mean	76.3

Temperature	Std Dev	2.2

(°F)	No. of Data Points	14





Exposure	Mean	37

Relative Humidity	Std Dev	3

(%)	No. of Data Points	14





Exposure	Mean	0.0

Static Pressure	Std Dev	0.0

(in H20)	No. of Data Points	14







1ACC Analytical Chamber Concentration



Table   SEQ Table \* ARABIC  3 .	  Exposure Conditions and Concentration
of [2-14C]DIPE/DIPE, Study B.

Analysis results

Treatment name: 		DIPE 3600 ppm Nose-Only Inhalation

Dpm/g of dose prep:	 	999562646.6 dpm/g

Molecular weight: 		102.18 

S/A comp/dose µCi: 		0.4503 µCi/mg

Exposure Summary

	Target  (ppm) 

Number of Open Ports	3600

125





ACC1 - Inlet	Daily mean	3529

(ppm)	Std Dev	40

	No. of Data Points	13





ACC - Exhaust	Daily mean	3357

(ppm)	Std Dev	130

	No. of Data Points	13





Exposure	Daily mean	72.3

Temperature	Std Dev	0.2

(°F)	No. of Data Points	13





Exposure	Daily mean	42

Relative Humidity	Std Dev	0

(%)	No. of Data Points	13





Exposure	Daily mean	-0.15

Static Pressure	Std Dev	0.0

(in H20)	No. of Data Points	13







1ACC Analytical Chamber Concentration

Table   SEQ Table \* ARABIC  4 .	  Exposure Conditions and
Concentration of [2-14C]DIPE/13CDIPE, Study C.

Analysis results

Treatment name: 		DIPE 3600 ppm Nose-Only Inhalation

Dpm/g of dose prep:	 	941599268.6 dpm/g

Molecular weight: 		108.18 

S/A comp/dose µCi: 		0.4241µCi/mg

Exposure Summary

	Target  (ppm) 

Number of Open Ports	3600

5





ACC1 - Inlet	Daily mean	3334

(ppm)	Std Dev	99

	No. of Data Points	13





ACC - Exhaust	Daily mean	1650

(ppm)	Std Dev	113

	No. of Data Points	12





Exposure	Daily mean	72.2

Temperature	Std Dev	0.2

(°F)	No. of Data Points	12





Exposure	Daily mean	42

Relative Humidity	Std Dev	0

(%)	No. of Data Points	12





Exposure	Daily mean	-0.15

Static Pressure	Std Dev	0.03

(in H20)	No. of Data Points	12







1ACC Analytical Chamber Concentration

Table   SEQ Table \* ARABIC  5 .	  Concentration of DIPE in blood from
male and female rats exposed to 3600 ppm DIPE.

	Male Rats	Female Rats

Time (hr)	DIPEa µg/mL in blood	DIPEa µg/mL in blood

	Mean	SD	Mean	SD

0.0833	19.298	5.1557	20.219	2.8453

0.1667	25.213	5.4138	29.693	4.3215

0.25	31.753	2.6903	31.596	4.0032

0.5	37.948	10.504	42.048	0.3598

1	44.554	6.6781	47.609	4.4577

2	48.719	7.9949	60.344	3.5563

4	55.708	2.4736	60.562	6.0246

6	47.557	17.696	65.61	5.5047

6.25	17.939	5.8199	18.672	1.1612

6.5	10.337	1.8071	12.058	2.5825

7	7.8988	0.6505	6.1304	0.8475

7.33	3.8405	1.3364	4.4085	0.606

8	2.2091	0.2765	1.9226	0.4641

10	0.5031	0.2859	0.387	0.0259

16	<LOQb	<LOQ	<LOQ	<LOQ

24	<LOQ	<LOQ	<LOQ	<LOQ



a Values are mean ± SD  of 3 animals. 

b Less than the limit of quantitation.

Table   SEQ Table \* ARABIC  6 .	  Concentration of Isopropanol in blood
from male and female rats exposed to 3600 ppm DIPE.

	Male Rats	Female Rats

Time (hr)	          Isopropanola µg/mL in blood	        Isopropanola 
µg/mL in blood

	Mean	SD	Mean	SD

0.0833	<LOQb	<LOQ	<LOQ	<LOQ

0.1667	2.655	0.3136	<LOQ	<LOQ

0.25	3.3402	0.2985	<LOQ	<LOQ

0.5	5.8764	1.0548	3.3292	0.1971

1	11.665	0.6519	5.1457	0.7126

2	22.367	4.2463	10.752	0.4521

4	42.303	3.8943	21.477	5.0914

6	66.182	8.3302	31.609	1.4026

6.25	63.386	6.378	35.708	4.836

6.5	63.394	7.4217	25.59	1.9423

7	50.948	6.6648	25.368	4.4118

7.33	43.933	5.1632	15.16	1.6226

8	31.884	3.6357	11.813	2.648

10	9.1135	0.6807	3.4767	0.1157

16	<LOQ	<LOQ	<LOQ	<LOQ

24	<LOQ	<LOQ	<LOQ	<LOQ



a Values are mean ± SD  of 3 animals. 

b Less than the limit of quantitation.Table   SEQ Table \* ARABIC  7 .	
 Concentration of Acetone in blood from male and female rats exposed to
3600 ppm DIPE.

	Male Rats	Female Rats

Time (hr)	        Acetonea µg/mL in blood	          Acetonea µg/mL in
blood

	Mean	SD	Mean	SD

0.0833	5.3986	0.9902	4.3126	2.0263

0.1667	8.6662	1.5401	5.0105	0.7406

0.25	12.545	2.4086	8.5253	1.8353

0.5	25.403	3.4346	16.779	4.5256

1	50.448	4.9173	36.046	1.9947

2	98.814	5.3419	70.829	5.0068

4	203.31	16.378	147.54	25.297

6	288.42	76.855	209.39	10.934

6.25	298.9	19.328	211.33	8.349

6.5	319.38	15.137	190.35	18.436

7	312.47	22.028	208.43	18.258

7.33	315.15	19.22	197.69	22.746

8	301.87	16.539	199.75	40.378

10	230.07	3.7206	115.47	4.5947

16	66.649	10.736	1.8999	0.0564

24	1.646	0.2375	2.7144b	n/a



a Values are mean ± SD  of 3 animals. 

bOne animal, with two Two animals with measurements less than the limit
of quantitation.Table   SEQ Table \* ARABIC  8 .	  Pharmacokinetic
Analysis of DIPE, Isopropanol and Acetone in male and female rats
exposed to 3600 ppm DIPE.

	Units	DIPE	DIPE	Isopropanol	Isopropanol	Acetone	Acetone



Male	Female	Male	Female	Male	Female

Cmax	µg /mL	55.7082	65.6099	66.1823	35.7084	319.3774	211.3721

Tmax	hr	4	6	6	6.25	6.5	6.25

Half Life	hr	0.9165	0.7587	1.1598	1.2261	2.3107	2.3195

Lambda z	1/hr	0.7563	0.9136	0.5653	0.5976	0.3	0.2988

AUCall	µg·hr/mL	311.6541	363.2418	338.858	156.0429	3208.097	1734.658









	

Table   SEQ Table \* ARABIC  9 .	  Total Recoverya of Radioactivity
following Exposure to 3600 ppm [2-14C]DIPE/DIPE

Rat	Total DPM Recovered	Total (Ci	Dose (mg)	Bodyweight (g)	Dose (mg/kg)
Mean Dose (mg/kg) c	SD d

BM-01	77199927	34.747	77.23	200.58	385.1	372.99	8.33 

BM-02	74997744	33.7828	75.03	203.03	369.6



BM-03	74152179	33.4019	74.18	202.66	366.1



BM-04	73329600	33.0314	73.36	197.58	371.3



CM-01	55226372	24.8767	58.6555.25	188.27	311.5293.5	317.89 299.45 
7.677.23

CM-02	57600304	25.9461	61.6757.63	187.41	326.4307.5



CM-03	61974740	27.9165	65.8262.00	208.47	315.7297.4



CM-04b	15313501	6.8980	16.2615.32	190.91	85.280.2





a Total recovery calculated from the total DPM recovered in all samples

b Total recovery for CM-04 does not include the analysis of exhaled
breath traps, which have been saved for other possible analysis. 

c Mean dose mg/kg indicates the mean of 4 rats for BM and the mean of 3
rats for  CM.  

d SD indicates the standard deviation of  the dose in mg/kg of 4 rats
for BM and of 3 rats for  CMTable   SEQ Table \* ARABIC  10 .	 
Recovery of Radioactivity in Carcass following Exposure to 3600 ppm
[2-14C]DIPE/DIPE (Group 2)

	Group 2 Study B	Group 2 Study B	Group 2 Study B	Group 2 Study B	Group 2
Study B	Group 2 Study B

Sample	BM-01	BM-02	BM-03	BM-04	Mean	SD

Nose Only Tube Rinse	0.22	0.17	0.24	0.16	0.199	0.037

Carcass Digest	98.20	97.75	99.53	98.73	98.552	0.764

Exhaled VOC	0.63	1.17	0.00	0.52	0.773	0.350

Exposure Urine	N.S.	N.S.	N.S.	N.S.	0.000	0.000

Exposure Feces	0.95	0.91	0.23	0.38	0.617	0.365

Exp. Urine Sample 2	N.S.-	N.S.-	N.S.-	0.21	0.052	0.105

Total	100.00	100.00	100.00	100.00	100.000	0.000



* Value is below 3 x background for the sample.aN.S. indicates no
sample.  

* Value is below 3 x background for the sample.

Table   SEQ Table \* ARABIC  11 .	  Recovery of Radioactivity in
Excreta and Carcass following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE
(Group 3)

	Group 3 Study Ca	Group 3 Study Ca	Group 3 Study Ca	Group 3 Study Ca
Group 3 Study Ca

	Male	Male	Male	 	 

Sample	CM-01	CM-02	CM-03	Mean	SD

Urine	5.5382	4.2344	4.9174	4.897	0.652

Feces	1.0493	0.8501	1.4376	1.112	0.299

CO2 Trap 1	17.5640	17.6930	19.5450	18.267	1.108

CO2 Trap 2	2.6872	1.1723	2.0266	1.962	0.760

Exhaled VOC Trap 1	64.7990	69.4660	68.0450	67.436	2.392

Exhaled VOC Trap 2	5.4380	3.8925	0.5220	3.284	2.514

Exposure Urine	N.S.	N.S.	N.S.	0.000	0.000

Exposure Feces	0.0198	N.S.	0.1172	0.046	0.063

Nose Only Tube Rinse	0.2170	0.1873	0.3494	0.251	0.086

Carcass Digest	2.6486	2.1383	3.0034	2.597	0.435

Cage Rinse	*0.0394	*0.0392	*0.0366	0.038	0.002

Total	100.00	100.00	100.00	100.000	0.000



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

bN.S. indicates no sample.

* Value is below 3 x background for the sample.Table   SEQ Table \*
ARABIC  12 .	  Recovery of Radioactivity in Urine following Exposure to
3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

Urine	0 - 8 h	3.0834	2.9938	2.9543	3.011	0.066

Urine	8 h - 24 h	2.0143	0.8914	1.6701	1.525	0.575

Urine	24 h - 48 h	0.2756	0.1731	0.1519	0.200	0.066

Urine	48 h - 72 h	0.0774	0.0797	0.0588	0.072	0.011

Urine	72 h - 96 h	0.0374	0.0448	0.0346	0.039	0.005

Urine	96 h - 120 h	0.0243	0.0231	0.0194	0.022	0.003

Urine	120 h - 144 h	0.0138	0.0141	0.0180	0.015	0.002

Urine	144 h - 168 h	0.0120	0.0144	0.0103	0.012	0.002

Subtotal

5.538	4.234	4.917	4.897	0.652



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.

Table   SEQ Table \* ARABIC  13 .	  Recovery of Radioactivity in Feces
following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

Feces	0 h - 24 h	0.5510	0.3695	0.8500	0.590	0.243

Feces	24 h - 48 h	0.1480	0.1845	0.2471	0.193	0.050

Feces	48 h - 72 h	0.1816	0.1262	0.0861	0.131	0.048

Feces	72 h - 96 h	0.0606	0.0490	0.1303	0.080	0.044

Feces	96 h - 120 h	0.0366	0.0521	0.0494	0.046	0.008

Feces	120 h - 144 h	0.0431	0.0343	0.0126	0.030	0.016

Feces	144 h - 168 h	0.0284	0.0345	0.0620	0.042	0.018

Subtotal

1.049	0.850	1.438	1.112	0.299



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.

Table   SEQ Table \* ARABIC  14 .	  Recovery of Radioactivity in CO2
Trap 1  following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

CO2 Trap 1	0-1 h	0.4472	0.4165	0.3813	0.415	0.033

CO2 Trap 1	1-3 h	*0.0174	1.1806	1.0756	0.758	0.643

CO2 Trap 1	3-6 h	3.0727	3.5843	3.5934	3.417	0.298

CO2 Trap 1	6-24 h	12.2670	11.2350	12.2830	11.928	0.600

CO2 Trap 1	24-48 h	0.8406	0.6149	1.1934	0.883	0.292

CO2 Trap 1	48-72 h	0.4159	0.2429	0.3996	0.353	0.096

CO2 Trap 1	72-96 h	0.1860	0.1479	0.2059	0.180	0.029

CO2 Trap 1	96-120 h	0.1496	0.1047	0.1822	0.146	0.039

CO2 Trap 1	120-144 h	0.1002	0.1007	0.1460	0.116	0.026

CO2 Trap 1	144-168 h	*0.0678	*0.0658	0.0841	0.073	0.010

Subtotal

17.564	17.693	19.545	18.267	1.108



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.

Table   SEQ Table \* ARABIC  15 .	  Recovery of Radioactivity in CO2
Trap 2 following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

CO2 Trap 2	0-1 h	*0.0006	*0.0021	*0.0019	0.002	0.001

CO2 Trap 2	1-3 h	1.2647	*0.0112	*0.0089	0.428	0.724

CO2 Trap 2	3-6 h	*0.0134	*0.0216	0.0273	0.021	0.007

CO2 Trap 2	6-24 h	0.9221	0.5623	1.2530	0.912	0.345

CO2 Trap 2	24-48 h	0.2068	0.2278	0.4163	0.284	0.115

CO2 Trap 2	48-72 h	0.1094	0.1368	0.1339	0.127	0.015

CO2 Trap 2	72-96 h	0.0584	0.0769	0.0691	0.068	0.009

CO2 Trap 2	96-120 h	0.0383	0.0673	0.0367	0.047	0.017

CO2 Trap 2	120-144 h	*0.0402	*0.0372	*0.0437	0.040	0.003

CO2 Trap 2	144-168 h	*0.0332	*0.0290	*0.0357	0.033	0.003

Subtotal

2.687	1.172	2.027	1.962	0.760



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.

Table   SEQ Table \* ARABIC  16 .	  Recovery of Radioactivity in Exhaled
VOC Trap 1 following exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

Exhaled VOC Trap 1	0-1 h	29.4100	34.3340	28.5230	30.756	3.131

Exhaled VOC Trap 1	1-3 h	18.2220	21.0790	19.8230	19.708	1.432

Exhaled VOC Trap 1	3-6 h	12.9700	12.7320	13.9460	13.216	0.643

Exhaled VOC Trap 1	6-24 h	4.1053	1.2148	5.6436	3.655	2.249

Exhaled VOC Trap 1	24-48 h	0.0488	0.0364	0.0668	0.051	0.015

Exhaled VOC Trap 1	48-72 h	0.0191	0.0258	0.0183	0.021	0.004

Exhaled VOC Trap 1	72-96 h	0.0090	0.0190	0.0098	0.013	0.006

Exhaled VOC Trap 1	96-120 h	*0.0062	0.0103	*0.0063	0.008	0.002

Exhaled VOC Trap 1	120-144 h	*0.0046	*0.0081	*0.0046	0.006	0.002

Exhaled VOC Trap 1	144-168 h	*0.0038	*0.0059	*0.0039	0.005	0.001

Subtotal

64.799	69.466	68.045	67.436	2.392



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.

 

Table   SEQ Table \* ARABIC  17 .	  Recovery of Radioactivity in Exhaled
VOC Trap 2 following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE (Group 3)



Group 3 Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3
Study CaGroup 3 Study C	Group 3 Study CaGroup 3 Study C	Group 3 Study
CaGroup 3 Study C



Male	Male	Male	 	 



CM-01	CM-02	CM-03	Mean	SD

Exhaled VOC Trap 2	0-1 h	*0.0017	*0.0030	*0.0028	0.003	0.001

Exhaled VOC Trap 2	1-3 h	*0.0033	*0.0040	*0.0039	0.004	0.000

Exhaled VOC Trap 2	3-6 h	*0.0013	*0.0058	*0.0048	0.004	0.002

Exhaled VOC Trap 2	6-24 h	5.4265	3.8723	0.0000	3.100	2.795

Exhaled VOC Trap 2	24-48 h	*0.0032	*0.0050	0.5099	0.173	0.292

Exhaled VOC Trap 2	48-72 h	*0.0007	*0.0007	*0.0003	0.001	0.000

Exhaled VOC Trap 2	72-96 h	*0.0006	*0.0005	0.0000	0.000	0.000

Exhaled VOC Trap 2	96-120 h	*0.0005	0.0003	0.0000	0.000	0.000

Exhaled VOC Trap 2	120-144 h	0.0001	*0.0006	0.0000	0.000	0.000

Exhaled VOC Trap 2	144-168 h	0.0002	*0.0002	0.0004	0.000	0.000

Subtotal

5.438	3.893	0.522	3.284	2.514



a CM-04 is excluded from the table, since exhaled breath traps were
saved for possible future analysis. 

* Value is below 3 x background for the sample.



Table   SEQ Table \* ARABIC  18 .	  Cumulative Recovery of Radioactivity
in Excreta and Carcass following Exposure to 3600 ppm
[2-14C]DIPE/13C6DIPE (Group 3)

Timepoint	CM-01	CM-02	CM-03	Mean	SD

0 ha	0.2368	0.1873	0.4667	0.297	0.149

1 h	30.0960	34.9430	29.3760	31.472	3.028

3 h	49.6040	57.2180	50.2870	52.370	4.213

6 h	65.6610	73.5620	67.8580	69.027	4.078

8 h	68.7440	76.5560	70.8130	72.037	4.047

24 h	94.0300	94.7010	92.5130	93.748	1.121

48 h	95.5530	95.9430	95.0980	95.531	0.423

72 h	96.3570	96.5550	95.7950	96.236	0.394

96 h	96.7090	96.8930	96.2450	96.616	0.334

120 h	96.9650	97.1510	96.5390	96.885	0.314

144 h	97.1670	97.3460	96.7640	97.092	0.298

168 h	100.0000	100.0000	100.0000	100.000	0.000

a Values at 0 h are from the samples collected at the end of the
inhalation exposure, incuding the nose only tube wash and any urine and
feces samples collected from the inhalation exposure.  



Table   SEQ Table \* ARABIC  19 .	  Recovery of Radioactivity in Tissues
from Rat CM-02 following Exposure to 3600 ppm [2-14C]DIPE/13C6DIPE
(Group 3)

Timepoint	Tissue	% of Dose in Tissue

CM-02               	Blood               	0.001

CM-02               	Spleen              	0.005

CM-02               	Liver               	0.119

CM-02               	Kidney              	0.024

CM-02               	Brain               	0.014

CM-02               	Heart               	0.007

CM-02               	Lung                	0.012

CM-02               	Stomach             	0.011

CM-02               	Small Intestine     	0.026

CM-02               	Femur               	0.006

CM-02               	Testes              	0.026

CM-02               	Cecum+Lg Int+Rect   	0.019

CM-02               	Adip (Abdominal)    	0.006

CM-02               	Cage Rinse          	0.039

CM-02               	Skin (Neck)         	0.005

CM-02               	Adipose (subcut)    	0.006

CM-02               	Stomach Contents    	0.001

CM-02               	Muscle Gastrocnemius	0.004

CM-02               	Small Intestine Contents	0.019



Table   SEQ Table \* ARABIC  20 .	  Normalized Recovery of Radioactivity
in Exposure B and C (Groups 2 and 3).  

Exposure	Mean Exposure Concentration (ppm)	Exposure Duration (hr)	Actual
ppm.hr	Recovered Dose (mg/kg)	Normalized Recovered Dose (mg/kg/ppm.hr)
Normalized % Recovered 

B	3529	6	21174	372.99	0.017615

	C	3334	5.66	18870	317.89	0.016846	95.6%



Figure   SEQ Figure \* ARABIC  1 .  Headspace GC-MS analysis of DIPE,
acetone and isopropanol in blood.

Selected ion monitoring with total ion chromatogram (top) and (in order)
acetone, 1-propanol (internal standard), DIPE, MTBE (internal standard)
and isopropanol.  



Figure   SEQ Figure \* ARABIC  2 .  Concentration of DIPE in male and
female rat blood during and following exposure to 3600 ppm DIPE for 6
hours.

Figure   SEQ Figure \* ARABIC  3 .  Concentration of Isopropanol in male
and female rat blood during and  following exposure to 3600 ppm DIPE for
6 hours.

Figure   SEQ Figure \* ARABIC  4 .  Concentration of Acetone  in male
and female blood during and following exposure to 3600 ppm DIPE for 6
hours.



Figure   SEQ Figure \* ARABIC  5 .  Noncompartmental analysis of DIPE in
male (top) and female (bottom) rat blood during and following exposure
to 3600 ppm DIPE for 6 hours.

Figure   SEQ Figure \* ARABIC  6 .  Noncompartmental analysis of
isopropanol in male (top) and female (bottom) rat blood during and
following exposure to 3600 ppm DIPE for 6 hours.

Figure   SEQ Figure \* ARABIC  7 .  Noncompartmental analysis of
acetone in male (top) and female (bottom) rat blood during and following
exposure to 3600 ppm DIPE for 6 hours.

Figure   SEQ Figure \* ARABIC  8 .  Cumulative Excretion of
Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps.

Appendix A

Approved Study Protocol, Amendments, and Deviations





RTI Protocol No. RTI-934 (RTI Project No. 020908.004001)

Deviations from the Approved Protocol

The deviations listed below did not affect the results of the study.

Deviation

For Study C, animals received 3600 ppm nose-only inhalation  exposures
for ca. five hours and forty minutes instead of six hours as stated in
the protocol.  Actual exposure animal exposure lengths for individual
animals are detailed in the study record.

Reason for the Deviation 

Insufficient volume of 14C DIPE/13C DIPE formulation was available for a
six-hour exposure.

Deviation

The protocol states (section 8.1) that:  “Cannula patency will be
maintained with daily flushings of heparinized saline (sterile saline
containing  20 IU/mL of sodium heparin).  Jugular cannulas will not be
flushed with heparinized saline prior to use on exposure day.  

Reason for the Deviation

The vendor (Charles River Laboratories) specified that the cannulas
retain patency best if the heparinized solution used to lock the cannula
is not disturbed until use (up through  one week prior to use).  

Deviation

Aliquots of the Study B and Study C inhalation formulatins were
transferred to a single vial  (for each formulation) already containing
20 mL of dimethylformamide instead of an empty vial.  Weights of )1
empty vial, 2) vial+DMF, and 3) weight of vial+DMF+formulation aliquot
were recorded in the process.  Aliquots of the DMF dilution wiere then
transferred to vials already containing scintillation cocktail for LSS
analysis instead of adding cocktail after the transfer.

 Reason for the Deviation

At the time, concern about evaporation of the DIPE formulation during
transfer to empty vials, thereby affecting quantiation results. 
Addition of DIPE formulation or the dilution to solvent was expected to
minimize evaporation.  

.Appendix B

Test Chemical Analysis Report



Appendix C

Test Chemical Analysis Report:  2-14C Diisopropyl ether

Test Chemical Analysis Report:  13C6-Diisopropyl ether

Analysis of Reference Substances: Acetone and Isopropanol

Appendix D

Method Validation for Analysis of DIPE, Isopropanol and Acetone



Appendix E

Pre-Study Inhalation Report

Appendix F

Inhalation Reports





Appendix G

Example CalculationsFormulae for Calculations

Formulae used in the Debra system for calculations are shown below:

Aliquot dpm/g is calculated by:

dpm/g = aliquot corrected count (dpm) / aliquot weight (g)

The mean of these aliquot figures for the sample is calculated by:

Mean dpm/g = Sum of all aliquot dpm/g / number of aliquots

The weight of the sample used for calculations is calculated from the
pot weight (before sample collection) and sample weight (weight of pot +
sample):

Weight of the sample = sample weight – pot weight

Depending on the nature of the sample processing, Effective weight may
be one of a number of values:

If processing type does not use homogenate (e.g. for urine, exhaled VOC
trap, CO2 trap, Cage Wash) then:

Effective weight = weight of the sample

If processing type uses homogenate (e.g. for feces and carcass) then:

Effective weight = Homogenate weight

To calculate the total dpm in the sample, Debra uses the previously
calculated figures;

Total Dpm = Mean dpm/g * Effective weight

For inhalation exposure, where the dpm administered is not precisely
known, the Dose Dpm is calculated as the sum of all dpm recovered for
each animal.

Recovery is calculated by:

Recovery = 100* (Total Dpm/ Dose Dpm)

Concentration is calculated by:

Concentration = (Total dpm/ effective weight) / (Specific activity)

Results are expressed in terms of the arithmetic mean ( standard
deviation. Mean values were calculated using:

 

Standard deviation was calculated using:

Example Calculations

Examples of the calculations for urine, feces, exhaled VOC trap, CO2
trap, and cage rinse made in the Debra™ system are shown below:

Subject		= CM-02

Tissue		= Urine

Timepoint	= 24 h

Aliquot 1 dpm/g	= 9129.865/0.0532

		= 171614.003759398 dpm/g

Aliquot 2 dpm/g	= 9167.455/0.053

		= 172970.849056604 dpm/g

Sum of dpm/g	= 344584.852816002 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 344584.852816002 / 2

		= 172292.426408001 dpm/g

		= 0.393762316049851 %

Recovery Effective Wt

		= Sample weight

		= 2.9801g

Concentration Effective Weight

		= Sample weight

		= 2.9801g

Total dpm		= Dpm/g x Recovery effective weight

		= 172292.426408001 x 2.9801

		= 513448.659938484 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (513448.659938484 / 57600304.4347919)

		= 100 x (0.00891399212168659)

		= 0.891399212168659%

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (513448.659938484 / 2.9801) / (0.4241438147 µCi/mg)

		= (172292.426408001 dpm/g) / (941599.268634 dpm/mg)

		= 182.978504919561 µg/g

Subject		= CM-02

Tissue		= Feces

Timepoint	= 24 h

Aliquot 1 dpm/g	= 1953.942/0.082

		= 23828.5609756098 dpm/g

Aliquot 2 dpm/g	= 2254.492/0.0927

		= 24320.3020496224 dpm/g

Sum of dpm/g	= 48148.8630252322 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 48148.8630252322 / 2

		= 24074.4315126161 dpm/g

Recovery Effective Weight

		= Homogenate weight

		= 8.8412g

Concentration Effective Weight

		= Sample weight

		= 4.24769999999999g

Total dpm		= Dpm/g x Recovery effective weight

		= 24074.4315126161 x 8.8412

		= 212846.863889341 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (212846.863889341 / 57600304.4347919)

		= 100 x (0.00369523852309324)

		= 0.369523852309324%

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (212846.863889341 / 4.24769999999999) / (0.4241438147 µCi/mg)

		= (50108.7326998945 dpm/g) / (941599.268634 dpm/mg)

		= 53.2166223669527 µg/g

Subject		= CM-02

Tissue		= Exhaled VOC Trap 1

Timepoint	= 1 h

Aliquot 1 dpm/g	= 121058.01375/0.0482

		= 2511577.04875519 dpm/g

Aliquot 2 dpm/g	= 121584.00375/0.0469

		= 2592409.46162047 dpm/g

Sum of dpm/g	= 5103986.51037566 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 5103986.51037566 / 2

		= 2551993.25518783 dpm/g

Recovery Effective Wt

		= Sample weight

		= 7.7495g

Concentration Effective Weight

		= Sample weight

		= 7.7495g

Total dpm		= Dpm/g x Recovery effective weight

		= 2551993.25518783 x 7.7495

		= 19776671.7310781 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (19776671.7310781 / 57600304.4347919)

		= 100 x (0.343343180650492)

		= 34.3343180650492%

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (19776671.7310781 / 7.7495) / (0.4241438147 µCi/mg)

		= (2551993.25518783 dpm/g) / (941599.268634 dpm/mg)

		= 2710.27531583586 µg/g

Subject		= CM-02

Tissue		= CO2 Trap 1

Timepoint	= 1 h

Aliquot 1 dpm/g	= 489.773333333333/1.064

		= 460.31328320802 dpm/g

Aliquot 2 dpm/g	= 470.083333333333/1.031

		= 455.94891690915 dpm/g

Sum of dpm/g	= 916.26220011717 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 916.26220011717 / 2

		= 458.131100058585 dpm/g

Recovery Effective Wt

		= Sample weight

		= 523.6g

Concentration Effective Weight

		= Sample weight

		= 523.6g

Total dpm		= Dpm/g x Recovery effective weight

		= 458.131100058585 x 523.6

		= 239877.443990675 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (239877.443990675 / 57600304.4347919)

		= 100 x (0.00416451694734071)

		= 0.416451694734071%

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (239877.443990675 / 523.6) / (0.4241438147 µCi/mg)

		= (458.131100058585 dpm/g) / (941599.268634 dpm/mg)

		= 0.486545726318592 µg/g

Subject		= CM-02

Tissue		= Exhaled VOC Trap 1

Timepoint	= 168 h

Aliquot 1 dpm/g	= 42.3866666666667/0.049

		= 865.034013605443 dpm/g

Aliquot 2 dpm/g	= 40.9566666666667/0.0464

		= 882.686781609196 dpm/g

Sum of dpm/g	= 1747.72079521464 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 1747.72079521464 / 2

		= 873.860397607319 dpm/g

Sum of (dpm/g)^2	= (Aliquot 1 dpm/g)^2 + .. + (Aliquot n dpm/g)^2

		= 1527419.79912194

SD of dpm/g	= Sqrt((n x Sum of (dpm/g)^2-(Sum of dpm/g)^2) / n(n-1))

		= Sqrt((Sum of (dpm/g)^2-((Sum of dpm/g)^2)/n) / (n-1))

		= Sqrt(1527419.79912194 - (3054527.97802569 / 2) / (2-1))

		= 12.4823919621806

Dpm/g %Variance (2 aliquot rule)

		= 100 x ((Mean dpm/g - aliquot 1 dpm/g) / Mean dpm/g)

		= 100 x ((873.860397607319 - 865.034013605443) / 873.860397607319)

		= 100 x 0.0101004508569603

		= 1.01004508569603 %

Recovery Effective Wt

		= Sample weight

		= 3.894g

Concentration Effective Weight

		= Sample weight

		= 3.894g

Total dpm		= Dpm/g x Recovery effective weight

		= 873.860397607319 x 3.894

		= 3402.8123882829 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (3402.8123882829 / 57600304.4347919)

		= 100 x (5.90762917257695E-5)

		= 0.00590762917257695%

Recovery SD	= Recovery x (dpm/g SD / dpm/g)

		= 0.00590762917257695 x (12.4823919621806 / 873.860397607319)

		= 0.00590762917257695 / 0.0142841945880121

		= 8.43857246549062E-5

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (3402.8123882829 / 3.894) / (0.4241438147 µCi/mg)

		= (873.860397607319 dpm/g) / (941599.268634 dpm/mg)

		= 0.928059766736065 µg/g

Concentration SD	= Concentration x (dpm/g SD / dpm/g)

		= 0.000928059766736065 mg/g x (12.4823919621806 / 873.860397607319)

		= 0.000928059766736065 / 0.0142841945880121

		= 0.0132565862973631

Subject		= CM-02

Tissue		= Cage Rinse

Timepoint	= 168 h

Aliquot 1 dpm/g	= 60.16/0.5662

		= 106.252207700459 dpm/g

Aliquot 2 dpm/g	= 67.4/0.5789

		= 116.427707721541 dpm/g

Sum of dpm/g	= 222.679915422 dpm/g

Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots

		= 222.679915422 / 2

		= 111.339957711 dpm/g

Recovery Effective Wt

		= Sample weight

		= 202.8g

Concentration Effective Weight

		= Sample weight

		= 202.8g

Total dpm		= Dpm/g x Recovery effective weight

		= 111.339957711 x 202.8

		= 22579.7434237908 dpm

Dose dpm (using Exposure Dose)

		= sum of all dpm recovered

		= 57600304.4347919 dpm

Recovery		= 100 x (Total dpm / Dose dpm)

		= 100 x (22579.7434237908 / 57600304.4347919)

		= 100 x (0.00039200736255401)

		= 0.039200736255401%

Recovery SD	= Recovery x (dpm/g SD / dpm/g)

		= 0.039200736255401 x (7.1951650668709 / 111.339957711)

		= 0.039200736255401 / 0.0646233860223573

		= 0.0025332843113934

Concentration	= (Total dpm/Concentration effective weight) / (Specific
activity)

		= (22579.7434237908 / 202.8) / (0.4241438147 µCi/mg)

		= (111.339957711 dpm/g) / (941599.268634 dpm/mg)

		= 0.118245586439891 µg/g





Appendix H

Raw Data Tables for Radioactivity

Sample Naming and Abbreviations

In the tables of raw data values in this appendix, the table headings
are derived from the conventions of sample naming used in the Debra(
system.  These are explained below.  Example calculations and formulae
are provided in Appendix G.

Column Heading	Source	Explanation

Subject

Animal number

Sample

The type of sample, e.g. urine, feces

Time

The time of sample collection

Pot wt	Balance	The weight of the empty sample container

Samp wt	Balance	Sample weight,  the weight of sample + empty sample
container

Corr Samp	Calculated	The corrected sample weight, calculated from Samp
wt – Pot wt

Homog wt	Balance	For samples requiring homogenization, the weight of pot
+ sample + medium for homogenization.  

Corr Homog	Calculated	Corrected Homogenate Weight, 

calculated from Homog Wt – Samp Wt.

Alq wt	Balance	Aliquot weight, weight of aliquot removed for
scintillation counting

Orig DPM	Scintillation Counter	Original DPM, the DPM measured in each
aliquot.

Bkg DPM	Scintillation Counter	The background DPM determined for the
batch of samples

Calc DPM	Calculated	The calculated DPM for the aliquot, = Orig DPM –
Calc DPM

LOD	Calculated	Limit of Detection.  If Orig DMP value is less than Bkg
DMP, then the sample is flagged with an *

LOQ	Calculated	Limit of Quantitation.  If Orig DMP value is less than 3
x Bkg DMP, then the sample is flagged with an *

DPM/g	Calculated	Calculated value of DPM/g sample.

Sample DPM	Calculated	Total DPM in the sample.

Reco (%)	Calculated	Percentage of the total recovered radioactivity
present in the sample.

Sample DPM Sum	Calculated	The sum of radioactivity in all samples for a
subject.

Table 1.  Preparation of 14C DIPE Formulation (Feedstock) for
Inhalation Exposure

14C DIPE for Study B

Ci/mg	(J)=(I)*1000

Nominal Specific Activity	38.76798779	Ci/mmol
(K)=(((H)*1000)/(G))*(B)





	Formulation Dilution









Weight of Feedstock 	0.0679	g	(L)

Weight of DMF	20.4687	g	(M)

Total weight of solution	20.5366	g	(N)=(L)+(M)





	Dose Formulation Dilution Aliquots



	Aliq #	Aliquot Wt (g)	DPM	DPM/g





	1	0.0876	301093	3437135

2	0.0862	291199	3378179

3	0.0955	295976	3099225





	Mean dilution DPM/g

	3304846

Ci/g	(R)=(Q)/2220000

Specific Activity (Ci/mg DIPE)	0.450253444	Ci/mg 
S)=(R)*(F)/(G)

Specific Activity (Ci/mmol DIPE)	46.00689695	Ci/mmol 
(T)=(R)*(B)/1000



Table 1 (contd).  Preparation of 14C DIPE Formulation (Feedstock) for
Inhalation Exposure

13C/14C DIPE For Study C

Ci/g	(R)=(Q)/2220000

Specific Activity (Ci/mg DIPE)	0.424143815	Ci/mg 
S)=(R)*(F)/(G)

Specific Activity (Ci/mmol DIPE)	45.88387787	Ci/mmol 
(T)=(R)*(B)/1000

Table 2.  Recovery of Radioactivity in Samples from Group B.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Homog wt	Corr Homog	Alq wt
Orig DPM	Bkg DPM	Calc DPM	LOD	LOQ	Mean DPM/g	Sample DPM	Recovery (%)

BM-01               

	Carcass Digest      	  0 h               

	109.00

	299.11

	190.11

	740.66

	631.66

	0.1074

0.1048	12678.60

12836.32	26.41

26.41	12652.190

12809.910	

	

	120018.171

	75810677.8347

	98.200



BM-01               

	Exhaled VOC         	  0 h               

	17.0963

	24.8570

	7.7607

	N.A.

	N.A.

	0.0447

0.0460	2854.75

2879.17	25.67

25.67	2829.084

2853.504	

	

	62661.577

	486297.7023

	0.630



BM-01               

	Exposure Urine      	  0 h               

	16.3491

	Missing

	Missing

	N.A.

	N.A.

	N.C.

N.C.	N.C.

N.C.	N.C.

N.C.	N.A.

N.A.	

	

	N.A.

	N.C.

	N.A.



BM-01               

	Exposure Feces      	  0 h               

	16.5629

	22.1174

	5.5545

	23.7509

	7.1880

	0.0636

0.0668	6646.67

6672.22	9.66

9.66	6637.007

6662.557	

	

	102047.161

	733514.9968

	0.950



BM-01               

	Nose Only Tube Rinse	  0 h               

	107.09

	301.24

	194.15

	N.A.

	N.A.

	0.4110

0.4885

0.4619	357.85

429.17

416.26	4.86

4.86

4.86	352.990

424.310

411.400	

	

	872.708

	169436.2046

	0.219



BM-02               

	Carcass Digest      	  0 h               	108.94

	303.89

	194.95

	751.53

	642.59

	0.1053

0.1150	11916.17

13281.38	26.41

26.41	11889.760

13254.970	

	

	114086.905

	73311103.9869

	97.751



BM-02               

	Exhaled VOC         	  0 h               

	17.3547

	25.0557

	7.7010

	N.A.

	N.A.

	0.0456

0.0468	5250.95

5340.78	25.67

25.67	5225.284

5315.114	

	

	114080.181

	878531.4760

	1.171



BM-02               

	Exposure Urine      	  0 h               

	16.5909

	Missing

	Missing

	N.A.

	N.A.

	N.C.

N.C.	N.C.

N.C.	N.C.

N.C.	N.A.

N.A.	

	

	N.A.

	N.C.

	N.A.



BM-02               

	Exposure Feces      	  0 h               

	16.3308

	20.9757

	4.6449

	22.5426

	6.2118

	0.1079

0.0662	12210.99

7020.68	9.66

9.66	12201.327

7011.017	

	

	109493.273

	680150.3155

	0.907



BM-02               

	Nose Only Tube Rinse	  0 h               

	108.03

	271.25

	163.22

	N.A.

	N.A.

	0.5193

0.4742

0.4911	404.39

367.04

406.95	4.86

4.86

4.86	399.530

362.180

402.090	



783.962

	127958.3311

	0.171



BM-03               

	Carcass Digest      	  0 h               

	108.55

	304.29

	195.74

	753.38

	644.83

	0.1089

0.1076	12673.66

12160.60	26.41

26.41	12647.250

12134.190	

	

	114453.823

	73803258.7380

	99.529



BM-03               

	Exhaled VOC         	  0 h               	17.2584	25.0178	7.7594	N.A.
N.A.	0.0474

0.0476	21.73

23.28	28.57

28.57	0.000

0.000	*

*	

	0.000

	0.0000

	0.000



BM-03               

	Exposure Urine      	  0 h               

	16.7684

	Missing

	Missing

	N.A.

	N.A.

	N.C.

N.C.	N.C.

N.C.	N.C.

N.C.	N.A.

N.A.	

	

	N.A.

	N.C.

	N.A.



BM-03               

	Exposure Feces      	  0 h               

	16.1935

	18.1833

	1.9898

	19.7737

	3.5802

	0.0723

0.0856	3400.14

4134.72	9.66

9.66	3390.477

4125.057	

	

	47542.237

	170210.7170

	0.230



BM-03               

	Nose Only Tube Rinse	  0 h               

	107.42

	261.91

	154.49

	N.A.

	N.A.

	0.6756

0.4754

0.5117	800.72

554.35

586.39	4.86

4.86

4.86	795.860

549.490

581.530	

	

	1156.773

	178709.8671

	0.241



BM-04               

	Carcass Digest      	  0 h               

	109.11

	296.36

	187.25

	719.52

	610.41

	0.0922

0.0927	11057.51

10924.22	26.41

26.41	11031.100

10897.810	

	

	118601.573

	72395586.0081

	98.726



BM-04               

	Exhaled VOC         	  0 h               

	17.2089

	25.0106

	7.8017

	N.A.

	N.A.

	0.0458

0.0448	2202.97

2249.47	25.67

25.67	2177.304

2223.804	

	

	48588.930

	379076.2542

	0.517



BM-04               

	Exposure Urine      	  0 h               

	16.6977

	Missing

	Missing

	N.A.

	N.A.

	N.C.

N.C.	N.C.

N.C.	N.C.

N.C.	N.A.

N.A.	

	

	N.A.

	N.C.

	N.A.



BM-04               

	Exposure Feces      	  0 h               

	16.7245

	20.0300

	3.3055

	23.1542

	6.4297

	0.0788

0.0934	3576.95

3938.10	9.66

9.66	3567.287

3928.437	

	

	43665.243

	280754.4101

	0.383



BM-04               

	Exp. Urine Sample 2 	  0 h               

	107.82

	121.65

	13.83

	625.14

	517.32

	0.9189

0.9323

0.6153	277.92

278.43

188.89	4.88

4.88

4.88	273.040

273.550

184.010	

	

	296.536

	153404.2432

	0.209



BM-04               

	Nose Only Tube Rinse

106.88

	184.10

	77.22

	N.A.

	N.A.

	0.4604

0.5673

0.6552	738.94

911.27

987.73	4.86

4.86

4.86	734.080

906.410

982.870

	1564.103

	120780.0023

	0.165





* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

Table 3.  Total Recovery of Radioactivity in Samples from Group B.  

Subject	Sample	Time	Sample DPM	Sample DPM Sum	Recovery (%)

1-01	Feces	0 h	127381.9731 dpm	59110333.860 dpm	0.215

1-01	Carcass Digest	0 h	58796748.8875 dpm

99.469

1-01	Exhaled VOC	0 h	1110.6238 dpm

0.002

1-01	Nose Only Tube Rinse	0 h	166155.5883 dpm

0.281

1-01	Transfer Bag Rinse	0 h	18936.7872 dpm

0.032

1-02	Feces	0 h	24901.9839 dpm	60334744.156 dpm	0.041

1-02	Carcass Digest	0 h	60107213.0993 dpm

99.623

1-02	Exhaled VOC	0 h	785.6933 dpm

0.001

1-02	Nose Only Tube Rinse	0 h	198731.0728 dpm

0.329

1-02	Transfer Bag Rinse	0 h	3112.3069 dpm

0.005

1-03	Feces	0 h	149317.0097 dpm	61168290.196 dpm	0.244

1-03	Carcass Digest	0 h	60412728.2023 dpm

98.765

1-03	Exhaled VOC	0 h	2464.3752 dpm

0.004

1-03	Nose Only Tube Rinse	0 h	260533.2472 dpm

0.426

1-03	Transfer Bag Rinse	0 h	343247.3620 dpm

0.561

1-04	Feces	0 h	830702.6192 dpm	49730780.503 dpm	1.670

1-04	Carcass Digest	0 h	48198191.8677 dpm

96.918

1-04	Exhaled VOC	0 h	8048.3908 dpm

0.016

1-04	Nose Only Tube Rinse	0 h	677265.1671 dpm

1.362

1-04	Transfer Bag Rinse	0 h	16572.4584 dpm

0.033



Subject 	Sample 	Time 	Sample dpm 	Sample dpm Sum	Reco (%) 

BM-01               	Carcass Digest	  0 h               	75810677.83 dpm
77199926.730 dpm 	98.200

BM-01               	Exhaled VOC	  0 h               	486297.70 dpm

0.630

BM-01               	Exposure Feces	  0 h               	733515.00 dpm

0.950

BM-01               	Nose Only Tube Rinse	  0 h               	169436.20
dpm

0.219

BM-02               	Carcass Digest	  0 h               	73311103.99 dpm
74997744.120 dpm 	97.751

BM-02               	Exhaled VOC	  0 h               	878531.48 dpm

1.171

BM-02               	Exposure Feces	  0 h               	680150.32 dpm

0.907

BM-02               	Nose Only Tube Rinse	  0 h               	127958.33
dpm

0.171

BM-03               	Carcass Digest	  0 h               	73803258.74 dpm
74152179.330 dpm 	99.529

BM-03               	Exhaled VOC	  0 h               	0.00 dpm

0.000

BM-03               	Exposure Feces	  0 h               	170210.72 dpm

0.230

BM-03               	Nose Only Tube Rinse	  0 h               	178709.87
dpm

0.241

BM-04               	Carcass Digest	  0 h               	72395586.01 dpm
73329600.910 dpm 	98.726

BM-04               	Exhaled VOC	  0 h               	379076.25 dpm

0.517

BM-04               	Exposure Feces	  0 h               	280754.41 dpm

0.383

BM-04               	Exp. Urine Sample 2	  0 h               	153404.24
dpm

0.209

BM-04               	Nose Only Tube Rinse	  0 h               	120780.00
dpm

0.165



Table 4.  Recovery of Radioactivity in Urine from Group C.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Urine               

	  8 h               

	16.3833 g

	20.0443 g

	3.6610 g

	0.0538 g

0.0535 g	25207.96

24753.04	25.83

25.83	25182.130

24727.210	

	

	468069.331

462190.841	1702841.2448  

	3.083

 

CM-01               

	Urine               

	 24 h               

	49.6715 g

	54.2445 g

	4.5730 g

	0.0546 g

0.0539 g	13386.21

13071.36	31.37

31.37	13354.845

13039.995	

	

	244594.231

241929.406	1112436.2962  

	2.014

 

CM-01               

	Urine               

	 48 h               

	49.8979 g

	54.5841 g

	4.6862 g

	0.1980 g

0.2073 g	6452.76

6718.38	4.60

4.60	6448.165

6713.785	

	

	32566.490

32386.807	152192.0689  

	0.276

 

CM-01               

	Urine               

	 72 h               

	50.0245 g

	57.9905 g

	7.9660 g

	0.2080 g

0.2110 g	1112.64

1144.74	3.90

3.90	1108.740

1140.840	

	

	5330.481

5406.825	42766.6875  

	0.077

 

CM-01               

	Urine               

	 96 h               

	49.4195 g

	58.9340 g

	9.5145 g

	0.2084 g

0.2055 g	448.37

457.20	3.90

3.90	444.470

453.300	

	

	2132.774

2205.839	20639.8664  

	0.037

 

CM-01               

	Urine               

	120 h               

	49.3183 g

	60.9000 g

	11.5817 g

	0.2033 g

0.2057 g	246.10

235.53	3.90

3.90	242.200

231.630	

	

	1191.343

1126.057	13419.7170  

	0.024

 

CM-01               

	Urine               

	144 h               

	49.4390 g

	58.4684 g

	9.0294 g

	0.2040 g

0.2054 g	163.49

181.32	0.00

0.00	163.490

181.320	

	

	801.422

882.765	7603.5986  

	0.014

 

CM-01               

	Urine               

	168 h               

	48.4712 g

	58.6314 g

	10.1602 g

	0.2080 g

0.2077 g	138.30

139.64	3.10

3.10	135.205

136.545	

	

	650.024

657.415	6641.9187  

	0.012

 

CM-02               

	Urine               

	  8 h               

	16.4290 g

	20.4321 g

	4.0031 g

	0.0542 g

0.0527 g	23333.85

22766.29	25.83

25.83	23308.020

22740.460	

	

	430037.269

431507.780	1724425.4933  

	2.994

 

CM-02               

	Urine               

	 24 h               

	49.6840 g

	52.6641 g

	2.9801 g

	0.0532 g

0.0530 g	9161.23

9198.82	31.37

31.37	9129.865

9167.455	

	

	171614.004

172970.849	513448.6599  	0.891

 

CM-02               

	Urine               

	 48 h               

	49.5056 g

	52.9815 g

	3.4759 g

	0.1035 g

0.1029 g	2965.31

2965.80	4.60

4.60	2960.715

2961.205	

	

	28605.942

28777.502	99729.5573  

	0.173

 

CM-02               

	Urine               

	 72 h               

	49.4267 g

	61.2787 g

	11.8520 g

	0.2068 g

0.2109 g	794.63

830.46	3.90

3.90	790.730

826.560	

	

	3823.646

3919.203	45884.1258  

	0.080

 

CM-02               

	Urine               

	 96 h               

	50.2654 g

	69.1980 g

	18.9326 g

	0.2001 g

0.2011 g	277.13

278.05	3.90

3.90	273.230

274.150	

	

	1365.467

1363.252	25830.8763  

	0.045

 

CM-02               

	Urine               

	120 h               

	49.7676 g

	58.2694 g

	8.5018 g

	0.2089 g

0.2121 g	336.87

329.49	3.90

3.90	332.970

325.590	

	

	1593.921

1535.078	13301.0590  

	0.023

 

CM-02               

	Urine               

	144 h               

	47.7846 g

	56.7403 g

	8.9557 g

	0.2044 g

0.2075 g	181.95

192.33	0.00

0.00	181.950

192.330	

	

	890.166

926.892	8136.5127  

	0.014

 

CM-02               

	Urine               

	168 h               

	50.0855 g

	60.5776 g

	10.4921 g

	0.2077 g

0.2101 g	161.69

174.21	3.10

3.10	158.595

171.115	

	

	763.577

814.446	8278.3864  

	0.014

 

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

Table 4 (contd).  Recovery of Radioactivity in Urine from Group 2.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	Urine               

	  8 h               

	16.5370 g

	21.0053 g

	4.4683 g

	0.0512 g

0.0517 g	20958.37

21257.53	25.83

25.83	20932.540

21231.700	

	

	408838.672

410671.180	1830907.9353  

	2.954

 

CM-03               

	Urine               

	 24 h               

	49.3539 g

	55.0547 g

	5.7008 g

	0.0518 g

0.0540 g	9358.26

9916.82	31.37

31.37	9326.895

9885.455	

	

	180055.888

183063.981	1035036.8761  

	1.670

 

CM-03               

	Urine               

	 48 h               

	50.0055 g

	59.6864 g

	9.6809 g

	0.1978 g

0.2022 g	1933.32

1965.51	4.60

4.60	1928.725

1960.915	

	

	9750.885

9697.898	94140.8610  

	0.152

 

CM-03               

	Urine               

	 72 h               

	49.5513 g

	62.8301 g

	13.2788 g

	0.2049 g

0.2116 g	578.91

570.88	3.90

3.90	575.010

566.980	

	

	2806.296

2679.490	36422.3233  

	0.059

 

CM-03               

	Urine               

	 96 h               

	49.3539 g

	64.2525 g

	14.8986 g

	0.2054 g

0.2046 g	296.89

301.67	3.90

3.90	292.990

297.770	

	

	1426.436

1455.376	21467.4863  

	0.035

 

CM-03               

	Urine               

	120 h               

	49.2192 g

	59.1509 g

	9.9317 g

	0.2087 g

0.2067 g	247.53

264.03	3.90

3.90	243.630

260.130	

	

	1167.369

1258.491	12046.4569  

	0.019

 

CM-03               

	Urine               

	144 h               

	50.0996 g

	62.7657 g

	12.6661 g

	0.2021 g

0.2055 g	181.35

176.72	0.00

0.00	181.350

176.720	

	

	897.328

859.951	11128.9383  

	0.018

 

CM-03               

	Urine               

	168 h               

	50.2428 g

	59.7059 g

	9.4631 g

	0.2064 g

0.2097 g	143.11

144.77	3.10

3.10	140.015

141.675	

	

	678.367

675.608	6406.4016  

	0.010

 

CM-04               

	Urine               

	  8 h               

	16.6114 g

	18.5065 g

	1.8951 g

	0.0529 g

0.0539 g	27836.60

27971.21	25.83

25.83	27810.770

27945.380	

	

	525723.440

518467.161	989422.8048  

	6.461

 

CM-04               

	Urine               

	 24 h               

	50.0264 g

	57.2613 g

	7.2349 g

	0.0542 g

0.0524 g	10002.06

9761.64	31.37

31.37	9970.695

9730.275	

	

	183961.162

185692.271	1337202.8125  

	8.732

 

CM-04               

	Urine               

	 48 h               

	49.1938 g

	65.1926 g

	15.9988 g

	0.2017 g

0.2051 g	2284.97

2395.29	4.60

4.60	2280.375

2390.695	

	

	11305.776

11656.241	183682.3569  	1.199

 

CM-04               

	Urine               

	 72 h               

	49.9395 g

	61.4514 g

	11.5119 g

	0.2071 g

0.2098 g	684.50

742.74	3.90

3.90	680.600

738.840	

	

	3286.335

3521.640	39186.3623  

	0.256

 

CM-04               

	Urine               

	 96 h               

	48.7565 g

	56.3028 g

	7.5463 g

	0.2121 g

0.2096 g	393.63

372.46	3.90

3.90	389.730

368.560	

	

	1837.482

1758.397	13567.7919  

	0.089

 

CM-04               

	Urine               

	120 h               

	49.9636 g

	60.1770 g

	10.2134 g

	0.2100 g

0.2111 g	251.37

243.74	3.90

3.90	247.470

239.840	

	

	1178.429

1136.144	11819.8278  

	0.077

 

CM-04               

	Urine               

	144 h               

	49.5018 g

	58.9107 g

	9.4089 g

	0.2049 g

0.2084 g	194.47

210.64	0.00

0.00	194.470

210.640	

	

	949.097

1010.749	9219.9960  

	0.060

 

CM-04               

	Urine               

	168 h               

	50.9518 g

	60.1408 g

	9.1890 g

	0.2091 g

0.2125 g	166.56

163.50	3.10

3.10	163.465

160.405	

	

	781.755

754.847	7059.9188  

	0.046

 



* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 



Table 5.  Recovery of Radioactivity in Feces from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Homog wt	Corr Homog	Alq wt
Orig DPM	Bkg DPM	Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Feces               

	 24 h               

	50.1379 

	55.4465 

	5.3086 

	60.6817 

	10.5438 

	0.0775 

0.0906 	2308.16

2566.50	16.42

16.42	2291.742

2550.082	

	

	29570.865

28146.600	304280.7035  	0.551

 

CM-01               

	Feces               

	 48 h               

	50.3414 

	54.0328 

	3.6914 

	57.8248 

	7.4834 

	0.0859 

0.0947 	962.37

1042.05	16.42

16.42	945.952

1025.632	

	

	11012.247

10830.327	81728.3597  	0.148

 

CM-01               

	Feces               

	 72 h               

	50.1662 

	58.1751 

	8.0089 

	65.3328 

	15.1666 

	0.0899 

0.0995 	669.00

609.90	16.42

16.42	652.582

593.482	

	

	7258.977

5964.643	100278.6765  	0.182

 

CM-01               

	Feces               

	 96 h               

	49.1753 

	55.0041 

	5.8288 

	61.1627 

	11.9874 

	0.0599 

0.0621 	176.87

182.11	9.08

9.08	167.788

173.028	

	

	2801.127

2786.272	33489.1935  	0.061

 

CM-01               

	Feces               

	120 h               

	50.2002 

	55.1973 

	4.9971 

	60.9793 

	10.7791 

	0.0731 

0.0547 	145.04

112.66	9.08

9.08	135.958

103.578	

	

	1859.884

1893.556	20229.3497  	0.037

 

CM-01               

	Feces               

	144 h               

	49.7822 

	60.6093 

	10.8271 

	72.6359 

	22.8537 

	0.0538 

0.0536 	65.59

64.40	9.08

9.08	56.508

55.318	

	

	1050.325

1032.043	23794.9089  	0.043

 

CM-01               

	Feces               

	168 h               

	50.0089 

	56.5155 

	6.5066 

	65.8127 

	15.8038 

	0.0567 

0.0546 	63.24

65.20	9.08

9.08	54.158

56.118	

	

	955.159

1027.793	15669.0866  	0.028

 

CM-02               

	Feces               

	 24 h               

	50.5312 

	54.7789 

	4.2477 

	59.3724 

	8.8412 

	0.0820 

0.0927 	1970.36

2270.91	16.42

16.42	1953.942

2254.492	

	

	23828.561

24320.302	212846.8639  	0.370

 

CM-02               

	Feces               

	 48 h               

	49.8609 

	53.3509 

	3.4900 

	57.3311 

	7.4702 

	0.0631 

0.0781 	901.67

1143.17	16.42

16.42	885.252

1126.752	

	

	14029.350

14427.042	106287.4716  	0.185

 

CM-02               

	Feces               

	 72 h               

	49.6047 

	61.2648 

	11.6601 

	75.0969 

	25.4922 

	0.0862 

0.0725 	255.68

228.62	16.42

16.42	239.262

212.202	

	

	2775.661

2926.924	72685.7237  	0.126

 

CM-02               

	Feces               

	 96 h               

	50.2877 

	56.0242 

	5.7365 

	66.1906 

	15.9029 

	0.0932 

0.0802 	169.07

155.96	9.08

9.08	159.988

146.878	

	

	1716.604

1831.390	28211.6997  	0.049

 

CM-02               

	Feces               

	120 h               

	49.6526 

	56.7563 

	7.1037 

	64.4761 

	14.8235 

	0.0433 

0.0472 	93.49

108.15	9.08

9.08	84.408

99.068	

	

	1949.365

2098.888	30004.6363  	0.052

 

CM-02               

	Feces               

	144 h               

	49.9225 

	62.9517 

	13.0292 

	73.9735 

	24.0510 

	0.0588 

0.0563 	60.96

51.89	9.08

9.08	51.878

42.808	

	

	882.270

760.346	19753.2879  	0.034

 

CM-02               

	Feces               

	168 h               

	49.9487 

	61.8468 

	11.8981 

	72.1372 

	22.1885 

	0.0562 

0.0623 	60.23

63.87	9.08

9.08	51.148

54.788	

	

	910.098

879.414	19853.2934  	0.034

 

Table 5 (contd).  Recovery of Radioactivity in Feces from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Homog wt	Corr Homog	Alq wt
Orig DPM	Bkg DPM	Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	Feces               

	 24 h               

	50.0987 

	57.2064 

	7.1077 

	61.1449 

	11.0462 

	0.0755 

0.0688 	3729.77

3194.62	16.42

16.42	3713.352

3178.202	

	

	49183.470

46194.797	526783.7049  	0.850

 

CM-03               

	Feces               

	 48 h               

	50.7997 

	58.1472 

	7.3475 

	66.0725 

	15.2728 

	0.0828 

0.0773 	964.40

681.73	16.42

16.42	947.982

665.312	

	

	11449.058

8606.882	153155.1821  	0.247

 

CM-03               

	Feces               

	 72 h               

	49.8413 

	56.3469 

	6.5056 

	64.7264 

	14.8851 

	0.0633 

0.0572 	231.90

231.98	16.42

16.42	215.482

215.562	

	

	3404.139

3768.566	53383.2190  	0.086

 

CM-03               

	Feces               

	 96 h               

	50.2371 

	60.9189 

	10.6818 

	70.5728 

	20.3357 

	0.0462 

0.0735 	232.63

237.32	9.08

9.08	223.548

228.238	

	

	4838.690

3105.272	80773.0200  	0.130

 

CM-03               

	Feces               

	120 h               

	50.1252 

	56.3624 

	6.2372 

	64.0774 

	13.9522 

	0.0568 

0.0510 	133.91

120.79	9.08

9.08	124.828

111.708	

	

	2197.667

2190.343	30611.1993  	0.049

 

CM-03               

	Feces               

	144 h               

	50.7243 

	52.3823 

	1.6580 

	57.2336 

	6.5093 

	0.0715 

0.0905 	98.58

113.16	9.08

9.08	89.498

104.078	

	

	1251.713

1150.028	7816.8261  	0.013

 

CM-03               

	Feces               

	168 h               

	49.9673 

	71.7209 

	21.7536 

	84.8118 

	34.8445 

	0.0780 

0.0563 	98.24

68.84	9.08

9.08	89.158

59.758	

	

	1143.045

1061.412	38406.6001  

	0.062

 

CM-04               

	Feces               

	 24 h               

	48.8431 

	53.9673 

	5.1242 

	58.0589 

	9.2158 

	0.0677 

0.0766 	2107.54

2386.85	16.42

16.42	2091.122

2370.432	

	

	30888.065

30945.587	284923.2872  

	1.861

 

CM-04               

	Feces               

	 48 h               

	49.6202 

	55.5099 

	5.8897 

	61.3325 

	11.7123 

	0.0709 

0.0863 	749.79

722.30	16.42

16.42	733.372

705.882	

	

	10343.752

8179.397	108474.3403  

	0.708

 

CM-04               

	Feces               

	 72 h               

	49.2083 

	56.6738 

	7.4655 

	65.2357 

	16.0274 

	0.0846 

0.0584 	230.38

187.77	16.42

16.42	213.962

171.352	

	

	2529.102

2934.110	43780.5359  

	0.286

 

CM-04               

	Feces               

	 96 h               

	49.8824 

	64.1021 

	14.2197 

	75.6956 

	25.8132 

	0.0669 

0.0458 	181.88

108.94	9.08

9.08	172.798

99.858	

	

	2582.922

2180.295	61476.9369  

	0.401

 

CM-04               

	Feces               

	120 h               

	49.3234 

	56.7203 

	7.3969 

	66.3387 

	17.0153 

	0.0470 

0.0558 	74.43

87.23	9.08

9.08	65.348

78.148	

	

	1390.372

1400.493	23743.7041  

	0.155

 

CM-04               

	Feces               

	144 h               

	48.8169 

	59.0513 

	10.2344 

	68.8185 

	20.0016 

	0.0608 

0.0514 	59.60

63.18	9.08

9.08	50.518

54.098	

	

	830.880

1052.481	18835.1115  

	0.123

 

CM-04               

	Feces               

	168 h               

	50.5895 

	60.6736 

	10.0841 

	71.0874 

	20.4979 

	0.0501 

0.0520 	50.21

51.19	9.08

9.08	41.128

42.108	

	

	820.908

809.760	16712.6327  

	0.109

 



* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

 

Table 6.  Recovery of Radioactivity in CO2 Trap 1 from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	CO2 Trap 1          

	  1 h               

	0.00 

	490.30 

	490.30 

	1.0077 

1.0011 	570.60

478.29	18.43

18.43	552.173

459.863	

	

	547.954

459.358	246942.5678  

	0.447

 

CM-01               

	CO2 Trap 1          

	  3 h               

	0.00 

	523.66 

	523.66 

	1.0389 

1.0392 	46.46

50.37	29.40

29.40	17.065

20.975	

	*

*	16.426

20.184	9585.5499  

	0.017

 

CM-01               

	CO2 Trap 1          

	  6 h               

	0.00 

	491.96 

	491.96 

	1.2911 

1.0336 	4759.31

3348.04	15.38

15.38	4743.929

3332.659	

	

	3674.331

3224.322	1696930.6986  

	3.073

 

CM-01               

	CO2 Trap 1          

	 24 h               

	0.00 

	500.33 

	500.33 

	1.0572 

1.0435 	14427.83

14047.58	15.38

15.38	14412.449

14032.199	

	

	13632.661

13447.244	6774444.4008  

	12.267

 

CM-01               

	CO2 Trap 1          

	 48 h               

	0.00 

	452.14 

	452.14 

	1.0312 

1.0924 	1007.16

1207.98	15.38

15.38	991.779

1192.599	

	

	961.772

1091.724	464233.7551  

	0.841

 

CM-01               

	CO2 Trap 1          

	 72 h               

	0.00 

	497.20 

	497.20 

	1.0415 

1.0380 	500.58

490.91	15.38

15.38	485.199

475.529	

	

	465.866

458.121	229702.9637  

	0.416

 

CM-01               

	CO2 Trap 1          

	 96 h               

	0.00 

	499.65 

	499.65 

	1.0526 

1.0451 	241.98

220.18	15.38

15.38	226.599

204.799	

	

	215.276

195.961	102737.2420  

	0.186

 

CM-01               

	CO2 Trap 1          

	120 h               

	0.01 

	511.23 

	511.22 

	1.0510 

1.0423 	180.24

188.74	15.38

15.38	164.859

173.359	

	

	156.859

166.324	82608.7736  

	0.150

 

CM-01               

	CO2 Trap 1          

	144 h               

	0.00 

	495.81 

	495.81 

	1.0236 

1.0339 	159.56

151.52	40.80

40.80	118.760

110.720	

	

	116.022

107.090	55310.4673  

	0.100

 

CM-01               

	CO2 Trap 1          

	168 h               

	0.00 

	432.25 

	432.25 

	1.0576 

1.0552 	146.06

133.70	48.32

48.32	97.737

85.377	

	*

*	92.414

80.910	37459.6609  

	0.068

 

CM-02               

	CO2 Trap 1          

	  1 h               

	0.00 

	523.60 

	523.60 

	1.0640 

1.0310 	508.20

488.51	18.43

18.43	489.773

470.083	

	

	460.313

455.949	239877.4440  

	0.416

 

CM-02               

	CO2 Trap 1          

	  3 h               

	0.00 

	504.82 

	504.82 

	1.0022 

1.0333 	1348.34

1431.13	18.43

18.43	1329.913

1412.703	

	

	1326.994

1367.176	680035.5272  

	1.181

 

CM-02               

	CO2 Trap 1          

	  6 h               

	0.00 

	503.45 

	503.45 

	1.1323 

1.0111 	4729.43

4098.53	15.38

15.38	4714.049

4083.149	

	

	4163.251

4038.324	2064541.3872  

	3.584

 

CM-02               

	CO2 Trap 1          

	 24 h               

	0.00 

	520.27 

	520.27 

	1.0500 

1.0381 	12921.11

13081.04	15.38

15.38	12905.729

13065.659	

	

	12291.171

12586.128	6471455.9649  

	11.235

 

CM-02               

	CO2 Trap 1          

	 48 h               

	0.00 

	503.79 

	503.79 

	1.2546 

1.0504 	870.87

775.99	15.38

15.38	855.489

760.609	

	

	681.882

724.114	354163.2880  

	0.615

 

CM-02               

	CO2 Trap 1          

	 72 h               

	0.00 

	540.28 

	540.28 

	1.0407 

1.0324 	292.56

275.18	15.38

15.38	277.179

259.799	

	

	266.339

251.646	139928.4295  

	0.243

 

CM-02               

	CO2 Trap 1          

	 96 h               

	0.00 

	503.82 

	503.82 

	1.0489 

1.0422 	195.67

188.68	15.38

15.38	180.289

173.299	

	

	171.884

166.282	85187.3860  

	0.148

 

CM-02               

	CO2 Trap 1          

	120 h               

	0.00 

	383.39 

	383.39 

	1.0480 

1.0314 	188.00

169.96	15.38

15.38	172.619

154.579	

	

	164.713

149.873	60304.5536  

	0.105

 

CM-02               

	CO2 Trap 1          

	144 h               

	0.00 

	481.47 

	481.47 

	1.0445 

1.0342 	161.63

170.29	40.80

40.80	120.830

129.490	

	

	115.682

125.208	57990.6625  

	0.101

 

CM-02               

	CO2 Trap 1          

	168 h               

	0.00 

	441.91 

	441.91 

	1.0512 

1.0547 	137.23

140.04	48.32

48.32	88.907

91.717	

	*

*	84.576

86.960	37901.8063  

	0.066

 

Table 6 (contd).  Recovery of Radioactivity in CO2 Trap 1 from Group C.
 

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	CO2 Trap 1          

	  1 h               

	0.00 

	526.18 

	526.18 

	1.0554 

1.0172 	491.89

475.81	18.43

18.43	473.463

457.383	

	

	448.610

449.649	236323.1407  

	0.381

 

CM-03               

	CO2 Trap 1          

	  3 h               

	0.00 

	468.45 

	468.45 

	1.0701 

1.0076 	1592.14

1404.32	18.43

18.43	1573.713

1385.893	

	

	1470.623

1375.440	666619.0295  

	1.076

 

CM-03               

	CO2 Trap 1          

	  6 h               

	0.00 

	491.87 

	491.87 

	1.3109 

1.3951 	5863.37

6424.76	15.38

15.38	5847.989

6409.379	

	

	4461.049

4594.208	2227004.5358  

	3.593

 

CM-03               

	CO2 Trap 1          

	 24 h               

	0.00 

	480.16 

	480.16 

	1.0451 

1.0455 	15663.79

17512.06	15.38

15.38	15648.409

17496.679	

	

	14973.121

16735.226	7612540.0951  

	12.283

 

CM-03               

	CO2 Trap 1          

	 48 h               

	0.00 

	537.25 

	537.25 

	1.1550 

0.9654 	1619.51

1332.57	15.38

15.38	1604.129

1317.189	

	

	1388.856

1364.397	739592.7459  

	1.193

 

CM-03               

	CO2 Trap 1          

	 72 h               

	0.00 

	475.62 

	475.62 

	1.0470 

1.0434 	572.84

546.39	15.38

15.38	557.459

531.009	

	

	532.435

508.922	247644.9995  

	0.400

 

CM-03               

	CO2 Trap 1          

	 96 h               

	0.00 

	499.88 

	499.88 

	1.0463 

1.0202 	296.67

262.08	15.38

15.38	281.289

246.699	

	

	268.842

241.814	127633.4003  

	0.206

 

CM-03               

	CO2 Trap 1          

	120 h               

	0.00 

	497.56 

	497.56 

	1.0396 

1.0529 	249.39

256.31	15.38

15.38	234.009

240.929	

	

	225.095

228.824	112926.1187  

	0.182

 

CM-03               

	CO2 Trap 1          

	144 h               

	0.00 

	457.74 

	457.74 

	1.0297 

1.0297 	242.00

246.60	40.80

40.80	201.200

205.800	

	

	195.397

199.864	90463.3291  

	0.146

 

CM-03               

	CO2 Trap 1          

	168 h               

	0.00 

	426.92 

	426.92 

	1.0598 

1.0556 	183.58

171.41	48.32

48.32	135.257

123.087	

	

	127.625

116.604	52132.9559  

	0.084

 

CM-04               

	CO2 Trap 1          

	  1 h               

	0.00 

	522.07 

	522.07 

	1.0378 

1.0418 	508.33

504.27	18.43

18.43	489.903

485.843	

	

	472.059

466.350	244957.6956  

	1.600

 

CM-04               

	CO2 Trap 1          

	  3 h               

	0.06 

	479.56 

	479.50 

	1.1495 

1.2601 	1653.86

2024.88	18.43

18.43	1635.433

2006.453	

	

	1422.735

1592.297	722853.7853  

	4.720

 

CM-04               

	CO2 Trap 1          

	  6 h               

	0.00 

	530.40 

	530.40 

	1.0388 

1.0498 	3363.69

3498.30	15.38

15.38	3348.309

3482.919	

	

	3223.247

3317.698	1734658.5733  

	11.328

 

CM-04               

	CO2 Trap 1          

	 24 h               

	0.00 

	484.93 

	484.93 

	1.0492 

1.0588 	12420.51

13959.27	15.38

15.38	12405.129

13943.889	

	

	11823.417

13169.521	6059912.7649  

	39.572

 

CM-04               

	CO2 Trap 1          

	 48 h               

	0.00 

	495.21 

	495.21 

	1.0911 

1.0175 	944.90

762.90	15.38

15.38	929.519

747.519	

	

	851.910

734.662	392843.3036  

	2.565

 

CM-04               

	CO2 Trap 1          

	 72 h               

	0.00 

	492.82 

	492.82 

	1.0427 

1.0333 	421.32

396.78	15.38

15.38	405.939

381.399	

	

	389.315

369.108	186883.0429  

	1.220

 

CM-04               

	CO2 Trap 1          

	 96 h               

	0.00 

	534.71 

	534.71 

	1.0459 

1.0354 	240.52

242.19	15.38

15.38	225.139

226.809	

	

	215.259

219.055	116115.8257  

	0.758

 

CM-04               

	CO2 Trap 1          

	120 h               

	0.00 

	514.48 

	514.48 

	1.0429 

1.0431 	189.01

177.93	15.38

15.38	173.629

162.549	

	

	166.487

155.833	82913.4703  

	0.541

 

CM-04               

	CO2 Trap 1          

	144 h               

	0.00 

	481.13 

	481.13 

	1.0371 

1.0425 	170.62

180.41	40.80

40.80	129.820

139.610	

	

	125.176

133.918	62329.0532  

	0.407

 

CM-04               

	CO2 Trap 1          

	168 h               

	0.00 

	447.61 

	447.61 

	1.0445 

1.0402 	150.64

134.50	48.32

48.32	102.317

86.177	

	*

*	97.958

82.846	40464.7951  

	0.264

 

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 



Table 7.  Recovery of Radioactivity in CO2 Trap 2 from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	CO2 Trap 2          

	  1 h               

	0.00 

	467.41 

	467.41 

	1.0360 

1.0249 	19.37

18.92	18.43

18.43	0.943

0.493	

	*

*	0.911

0.481	325.2943  

	0.001

 

CM-01               

	CO2 Trap 2          

	  3 h               

	0.00 

	494.91 

	494.91 

	1.0448 

1.0472 	1523.93

1487.19	29.40

29.40	1494.535

1457.795	

	

	1430.451

1392.088	698451.4452  

	1.265

 

CM-01               

	CO2 Trap 2          

	  6 h               

	0.00 

	500.60 

	500.60 

	0.8320 

1.0826 	24.58

35.51	15.38

15.38	9.199

20.129	

	*

*	11.057

18.593	7421.3663  

	0.013

 

CM-01               

	CO2 Trap 2          

	 24 h               

	0.00 

	480.62 

	480.62 

	1.0296 

1.0314 	1111.84

1102.61	15.38

15.38	1096.459

1087.229	

	

	1064.937

1054.129	509232.8427  

	0.922

 

CM-01               

	CO2 Trap 2          

	 48 h               

	0.00 

	485.06 

	485.06 

	1.0431 

1.0131 	262.34

252.68	15.38

15.38	246.959

237.299	

	

	236.755

234.231	114228.1428  

	0.207

 

CM-01               

	CO2 Trap 2          

	 72 h               

	0.00 

	500.26 

	500.26 

	1.0470 

1.0260 	137.03

144.06	15.38

15.38	121.649

128.679	

	

	116.188

125.418	60433.0240  

	0.109

 

CM-01               

	CO2 Trap 2          

	 96 h               

	0.01 

	550.29 

	550.28 

	1.0437 

1.0423 	78.87

74.13	15.38

15.38	63.489

58.749	

	

	60.831

56.365	32245.2092  

	0.058

 

CM-01               

	CO2 Trap 2          

	120 h               

	0.00 

	529.51 

	529.51 

	1.0278 

1.0170 	59.03

53.50	15.38

15.38	43.649

38.119	

	

	42.468

37.482	21167.2592  

	0.038

 

CM-01               

	CO2 Trap 2          

	144 h               

	0.00 

	496.85 

	496.85 

	1.0352 

1.0031 	94.44

85.95	40.80

48.32	53.640

37.627	

	*

*	51.816

37.510	22190.9255  

	0.040

 

CM-01               

	CO2 Trap 2          

	168 h               

	0.00 

	423.49 

	423.49 

	1.0497 

1.0511 	95.33

92.32	48.32

48.32	47.007

43.997	

	*

*	44.781

41.858	18345.3295  

	0.033

 

CM-02               

	CO2 Trap 2          

	  1 h               

	0.00 

	571.59 

	571.59 

	1.0299 

1.0281 	22.36

18.92	18.43

18.43	3.933

0.493	

	*

*	3.819

0.480	1228.6300  

	0.002

 

CM-02               

	CO2 Trap 2          

	  3 h               

	0.00 

	507.47 

	507.47 

	1.1457 

1.0445 	32.47

32.25	18.43

18.43	14.043

13.823	

	*

*	12.257

13.234	6468.1692  

	0.011

 

CM-02               

	CO2 Trap 2          

	  6 h               

	0.01 

	548.70 

	548.69 

	1.0659 

1.0745 	40.36

38.96	15.38

15.38	24.979

23.579	

	*

*	23.435

21.944	12449.4979  

	0.022

 

CM-02               

	CO2 Trap 2          

	 24 h               

	0.00 

	480.57 

	480.57 

	1.0380 

1.0382 	710.86

719.07	15.38

15.38	695.479

703.689	

	

	670.018

677.797	323859.8783  

	0.562

 

CM-02               

	CO2 Trap 2          

	 48 h               

	0.00 

	596.52 

	596.52 

	0.9346 

1.0249 	217.10

245.07	15.38

15.38	201.719

229.689	

	

	215.835

224.109	131217.5367  

	0.228

 

CM-02               

	CO2 Trap 2          

	 72 h               

	0.00 

	526.52 

	526.52 

	1.0378 

1.0208 	175.16

163.67	15.38

15.38	159.779

148.289	

	

	153.959

145.268	78774.4871  

	0.137

 

CM-02               

	CO2 Trap 2          

	 96 h               

	0.00 

	519.50 

	519.50 

	1.0404 

1.0380 	107.02

101.02	15.38

15.38	91.639

85.639	

	

	88.081

82.504	44309.3432  

	0.077

 

CM-02               

	CO2 Trap 2          

	120 h               

	0.00 

	539.26 

	539.26 

	1.0359 

1.0388 	90.59

89.39	15.38

15.38	75.209

74.009	

	

	72.603

71.245	38785.5875  

	0.067

 

CM-02               

	CO2 Trap 2          

	144 h               

	0.05 

	466.00 

	465.95 

	1.0233 

1.0246 	86.46

89.29	40.80

40.80	45.660

48.490	

	*

*	44.620

47.326	21421.1500  

	0.037

 

CM-02               

	CO2 Trap 2          

	168 h               

	0.00 

	446.26 

	446.26 

	1.0401 

1.0393 	93.68

80.83	48.32

48.32	45.357

32.507	

	*

*	43.608

31.277	16709.1902  

	0.029

 

Table 7 (contd).  Recovery of Radioactivity in CO2 Trap 2 from Group C.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	CO2 Trap 2          

	  1 h               

	0.00 

	521.17 

	521.17 

	1.0485 

1.0273 	18.69

22.82	18.43

18.43	0.263

4.393	

	*

*	0.251

4.277	1179.8598  

	0.002

 

CM-03               

	CO2 Trap 2          

	  3 h               

	0.00 

	493.38 

	493.38 

	1.1244 

1.0920 	31.80

29.95	18.43

18.43	13.373

11.523	

	*

*	11.894

10.553	5537.2663  

	0.009

 

CM-03               

	CO2 Trap 2          

	  6 h               

	0.00 

	490.60 

	490.60 

	1.0724 

1.1990 	52.79

56.31	15.38

15.38	37.409

40.929	

	

	34.884

34.136	16930.4947  

	0.027

 

CM-03               

	CO2 Trap 2          

	 24 h               

	0.00 

	483.12 

	483.12 

	1.0375 

1.0375 	1691.43

1674.66	15.38

15.38	1676.049

1659.279	

	

	1615.469

1599.305	776560.8440  

	1.253

 

CM-03               

	CO2 Trap 2          

	 48 h               

	0.00 

	525.06 

	525.06 

	1.0157 

1.0333 	500.41

537.45	15.38

15.38	485.029

522.069	

	

	477.532

505.244	258008.2599  

	0.416

 

CM-03               

	CO2 Trap 2          

	 72 h               

	0.00 

	533.66 

	533.66 

	1.0400 

1.0266 	186.17

166.03	15.38

15.38	170.789

150.649	

	

	164.220

146.746	82975.0407  

	0.134

 

CM-03               

	CO2 Trap 2          

	 96 h               

	0.00 

	534.21 

	534.21 

	1.0271 

1.0309 	96.23

99.43	15.38

15.38	80.849

84.049	

	

	78.716

81.530	42802.4303  

	0.069

 

CM-03               

	CO2 Trap 2          

	120 h               

	0.00 

	499.09 

	499.09 

	1.0322 

1.0397 	60.01

65.28	15.38

15.38	44.629

49.899	

	

	43.237

47.994	22766.1409  

	0.037

 

CM-03               

	CO2 Trap 2          

	144 h               

	0.00 

	434.99 

	434.99 

	1.0310 

1.0316 	100.62

109.29	40.80

40.80	59.820

68.490	

	*

*	58.021

66.392	27059.2818  

	0.044

 

CM-03               

	CO2 Trap 2          

	168 h               

	0.00 

	463.41 

	463.41 

	1.0418 

1.0509 	97.90

98.78	48.32

48.32	49.577

50.457	

	*

*	47.588

48.013	22151.0729  

	0.036

 

CM-04               

	CO2 Trap 2          

	  1 h               

	0.00 

	506.47 

	506.47 

	1.0202 

1.1229 	18.23

19.42	18.43

18.43	0.000

0.993	*

*	

	0.000

0.885	224.0153  

	0.001

 

CM-04               

	CO2 Trap 2          

	  3 h               

	0.00 

	470.22 

	470.22 

	1.0450 

1.1401 	25.34

22.15	18.43

18.43	6.913

3.723	

	*

*	6.616

3.266	2323.2219  

	0.015

 

CM-04               

	CO2 Trap 2          

	  6 h               

	0.00 

	507.89 

	507.89 

	1.0146 

1.0599 	41.43

36.22	15.38

15.38	26.049

20.839	

	*

*	25.674

19.661	11512.7544  

	0.075

 

CM-04               

	CO2 Trap 2          

	 24 h               

	0.00 

	498.50 

	498.50 

	1.0329 

1.0390 	1334.77

1321.62	15.38

15.38	1319.389

1306.239	

	

	1277.364

1257.208	631742.0214  

	4.125

 

CM-04               

	CO2 Trap 2          

	 48 h               

	0.00 

	503.19 

	503.19 

	1.0357 

1.0142 	306.46

313.37	15.38

15.38	291.079

297.989	

	

	281.046

293.817	144632.5680  

	0.944

 

CM-04               

	CO2 Trap 2          

	 72 h               

	0.00 

	497.60 

	497.60 

	1.0417 

1.0332 	164.92

149.96	15.38

15.38	149.539

134.579	

	

	143.553

130.255	68123.3236  

	0.445

 

CM-04               

	CO2 Trap 2          

	 96 h               

	0.00 

	500.89 

	500.89 

	1.0382 

1.0325 	84.11

92.55	15.38

15.38	68.729

77.169	

	

	66.200

74.740	35297.7887  

	0.231

 

CM-04               

	CO2 Trap 2          

	120 h               

	0.00 

	503.19 

	503.19 

	1.0374 

1.0343 	57.23

75.47	15.38

15.38	41.849

60.089	

	

	40.340

58.096	24766.1932  

	0.162

 

CM-04               

	CO2 Trap 2          

	144 h               

	0.00 

	460.40 

	460.40 

	1.0349 

1.0484 	85.61

78.99	40.80

40.80	44.810

38.190	

	*

*	43.299

36.427	18352.8805  

	0.120

 

CM-04               

	CO2 Trap 2          

	168 h               

	0.00 

	431.17 

	431.17 

	1.0396 

1.0489 	85.88

84.29	48.32

48.32	37.557

35.967	

	*

*	36.126

34.290	15180.6258  

	0.099

 



* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

Table 8.  Recovery of Radioactivity in Exhaled VOC Trap 1 from Group C.
 

Subjecta	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Exhaled VOC Trap 1  	  1 h               

	17.5558 

	25.3023 

	7.7465 

	0.0474 

0.0483 	99943.74

100749.81	25.67

25.67	99918.074

100724.144	

	

	2107976.239

2085385.999	16241940.2899  

	29.410

 

CM-01               

	Exhaled VOC Trap 1  	  3 h               

	17.5676 

	25.3483 

	7.7807 

	0.0460 

0.0474 	59579.64

61273.30	25.67

25.67	59553.974

61247.634	

	

	1294651.603

1292144.172	10063540.9441  

	18.222

 

CM-01               

	Exhaled VOC Trap 1  	  6 h               

	17.5313 

	25.3044 

	7.7731 

	0.0476 

0.0482 	44284.21

44039.05	25.67

25.67	44258.544

44013.384	

	

	929801.339

913140.742	7162686.5449  

	12.970

 

CM-01               

	Exhaled VOC Trap 1  	 24 h               

	17.6593 

	25.4422 

	7.7829 

	0.0469 

0.0480 	13796.80

13896.70	25.67

25.67	13771.134

13871.034	

	

	293627.585

288979.870	2267187.7811  

	4.105

 

CM-01               

	Exhaled VOC Trap 1  	 48 h               

	17.6284 

	21.4364 

	3.8080 

	0.0497 

0.0485 	378.90

367.05	25.59

25.59	353.308

341.458	

	

	7108.803

7040.361	26940.0076  

	0.049

 

CM-01               

	Exhaled VOC Trap 1  	 72 h               

	17.6258 

	21.4358 

	3.8100 

	0.0484 

0.0494 	156.32

165.32	25.59

25.59	130.728

139.728	

	

	2700.981

2828.492	10533.6467  

	0.019

 

CM-01               

	Exhaled VOC Trap 1  	 96 h               

	17.6580 

	21.5898 

	3.9318 

	0.0458 

0.0480 	90.47

81.26	26.58

26.58	63.886

54.676	

	

	1394.891

1139.083	4981.5398  

	0.009

 

CM-01               

	Exhaled VOC Trap 1  	120 h               

	17.7819 

	21.7156 

	3.9337 

	0.0477 

0.0508 	70.95

67.63	26.58

26.58	44.366

41.046	

	*

*	930.105

807.992	3418.5760  

	0.006

 

CM-01               

	Exhaled VOC Trap 1  	144 h               

	17.4693 

	21.3647 

	3.8954 

	0.0492 

0.0482 	57.05

59.98	26.58

26.58	30.466

33.396	

	*

*	619.228

692.863	2555.5591  

	0.005

 

CM-01               

	Exhaled VOC Trap 1  	168 h               

	17.7322 

	21.6433 

	3.9111 

	0.0459 

0.0485 	51.39

50.39	25.67

25.67	25.717

24.717	

	*

*	560.276

509.622	2092.2389  

	0.004

 

CM-02               

	Exhaled VOC Trap 1  	  1 h               

	17.5459 

	25.2954 

	7.7495 

	0.0482 

0.0469 	121083.68

121609.67	25.67

25.67	121058.014

121584.004	

	

	2511577.049

2592409.462	19776671.7311  

	34.334

 

CM-02               

	Exhaled VOC Trap 1  	  3 h               

	17.5840 

	25.3323 

	7.7483 

	0.0472 

0.0491 	73991.88

76960.98	25.67

25.67	73966.214

76935.314	

	

	1567080.800

1566910.667	12141553.0411  

	21.079

 

CM-02               

	Exhaled VOC Trap 1  	  6 h               

	17.4309 

	25.1783 

	7.7474 

	0.0474 

0.0493 	45609.96

45949.57	25.67

25.67	45584.294

45923.904	

	

	961693.961

931519.346	7333740.3866  

	12.732

 

CM-02               

	Exhaled VOC Trap 1  	 24 h               

	17.5774 

	25.3569 

	7.7795 

	0.0475 

0.0472 	4309.84

4259.25	25.67

25.67	4284.174

4233.584	

	

	90193.132

89694.571	699718.1910  

	1.215

 

CM-02               

	Exhaled VOC Trap 1  	 48 h               

	17.5024 

	21.3221 

	3.8197 

	0.0488 

0.0492 	303.20

285.14	25.59

25.59	277.608

259.548	

	

	5688.678

5275.356	20939.6603  

	0.036

 

CM-02               

	Exhaled VOC Trap 1  	 72 h               

	17.7206 

	21.5519 

	3.8313 

	0.0485 

0.0478 	214.15

210.72	25.59

25.59	188.558

185.128	

	

	3887.784

3872.960	14866.8688  

	0.026

 

CM-02               

	Exhaled VOC Trap 1  	 96 h               

	17.6396 

	21.5424 

	3.9028 

	0.0479 

0.0464 	151.99

165.19	26.58

26.58	125.406

138.606	

	

	2618.079

2987.198	10938.1387  

	0.019

 

CM-02               

	Exhaled VOC Trap 1  	120 h               

	17.8302 

	21.7374 

	3.9072 

	0.0472 

0.0477 	99.39

98.53	26.58

26.58	72.806

71.946	

	

	1542.500

1508.302	5960.0466  

	0.010

 

CM-02               

	Exhaled VOC Trap 1  	144 h               

	17.6197 

	21.5368 

	3.9171 

	0.0470 

0.0471 	76.54

89.14	26.58

26.58	49.956

62.556	

	*

*	1062.894

1328.153	4682.9841  

	0.008

 

CM-02               

	Exhaled VOC Trap 1  	168 h               

	17.9646 

	21.8586 

	3.8940 

	0.0490 

0.0464 	68.06

66.63	25.67

25.67	42.387

40.957	

	*

*	865.034

882.687	3402.8124  

	0.006

 

a Samples from CM-04 were not analyzed.

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. Table 8 (contd).  Recovery of Radioactivity in Exhaled VOC
Trap 1 from Group C.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	Exhaled VOC Trap 1  

	  1 h               

	17.4816 

	25.5681 

	8.0865 

	0.0471 

0.0462 	103897.22

100125.02	25.67

25.67	103871.554

100099.354	

	

	2205340.844

2166652.679	17677062.8099  

	28.523

 

CM-03               

	Exhaled VOC Trap 1  	  3 h               

	17.5195 

	25.2592 

	7.7397 

	0.0457 

0.0492 	74391.22

76154.17	25.67

25.67	74365.554

76128.504	

	

	1627255.005

1547327.312	12285157.3812  

	19.823

 

CM-03               

	Exhaled VOC Trap 1  	  6 h               

	17.6374 

	25.3807 

	7.7433 

	0.0479 

0.0469 	53799.01

52072.05	25.67

25.67	53773.344

52046.384	

	

	1122616.780

1109730.997	8642869.2691  

	13.946

 

CM-03               

	Exhaled VOC Trap 1  	 24 h               

	17.9299 

	25.7339 

	7.8040 

	0.0486 

0.0497 	22022.07

22080.24	25.67

25.67	21996.404

22054.574	

	

	452600.900

443753.999	3497576.8167  

	5.644

 

CM-03               

	Exhaled VOC Trap 1  	 48 h               

	17.6796 

	21.4889 

	3.8093 

	0.0478 

0.0484 	545.00

551.15	25.59

25.59	519.408

525.558	

	

	10866.266

10858.626	41378.3150  

	0.067

 

CM-03               

	Exhaled VOC Trap 1  	 72 h               

	17.6713 

	21.4801 

	3.8088 

	0.0490 

0.0484 	167.96

173.29	25.59

25.59	142.368

147.698	

	

	2905.459

3051.601	11344.6259  

	0.018

 

CM-03               

	Exhaled VOC Trap 1  	 96 h               

	17.7283 

	21.6241 

	3.8958 

	0.0486 

0.0483 	102.20

101.46	26.58

26.58	75.616

74.876	

	

	1555.885

1550.228	6050.3966  

	0.010

 

CM-03               

	Exhaled VOC Trap 1  	120 h               

	17.5743 

	21.4510 

	3.8767 

	0.0453 

0.0449 	71.37

72.05	26.58

26.58	44.786

45.466	

	*

*	988.653

1012.606	3879.1408  

	0.006

 

CM-03               

	Exhaled VOC Trap 1  	144 h               

	17.5994 

	21.5116 

	3.9122 

	0.0457 

0.0481 	62.68

59.05	26.58

26.58	36.096

32.466	

	*

*	789.847

674.969	2865.3259  

	0.005

 

CM-03               

	Exhaled VOC Trap 1  	168 h               

	17.7335 

	21.6304 

	3.8969 

	0.0458 

0.0480 	48.47

61.56	25.67

25.67	22.797

35.887	

	*

*	497.744

747.639	2426.5659  

	0.004

 

a Samples from CM-04 were not analyzed.

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

Table 9.  Recovery of Radioactivity in VOC Trap 2 from Group C.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Exhaled VOC Trap 2  	  1 h               

	17.2870 

	25.0071 

	7.7201 

	0.0473 

0.0459 	31.00

31.97	25.67

25.67	5.334

6.304	

	*

*	112.764

137.337	965.4019  

	0.002

 

CM-01               

	Exhaled VOC Trap 2  	  3 h               

	17.3408 

	25.1146 

	7.7738 

	0.0472 

0.0474 	39.11

34.60	25.67

25.67	13.444

8.934	

	*

*	284.825

188.476	1839.6735  

	0.003

 

CM-01               

	Exhaled VOC Trap 2  	  6 h               

	17.4090 

	25.1304 

	7.7214 

	0.0476 

0.0453 	34.18

25.69	25.67

25.67	8.514

0.024	

	*

*	178.860

0.524	692.5500  

	0.001

 

CM-01               

	Exhaled VOC Trap 2  	 24 h               

	17.6242 

	25.4035 

	7.7793 

	0.0456 

0.0483 	18230.11

17956.97	25.67

25.67	18204.444

17931.304	

	

	399220.258

371248.525	2996853.8999  

	5.426

 

CM-01               

	Exhaled VOC Trap 2  	 48 h               

	17.7448 

	21.5501 

	3.8053 

	0.0477 

0.0479 	51.12

44.42	25.59

25.59	25.528

18.828	

	*

*	535.168

393.058	1766.0895  

	0.003

 

CM-01               

	Exhaled VOC Trap 2  	 72 h               

	17.7050 

	21.5138 

	3.8088 

	0.0483 

0.0489 	30.73

30.07	25.59

25.59	5.138

4.478	

	*

*	106.366

91.564	376.9396  

	0.001

 

CM-01               

	Exhaled VOC Trap 2  	 96 h               

	17.4716 

	21.3689 

	3.8973 

	0.0486 

0.0461 	30.75

31.00	26.58

26.58	4.166

4.416	

	*

*	85.720

95.792	353.7032  

	0.001

 

CM-01               

	Exhaled VOC Trap 2  	120 h               

	17.6334 

	21.5254 

	3.8920 

	0.0470 

0.0473 	31.23

28.06	26.58

26.58	4.646

1.476	

	*

*	98.851

31.205	253.0892  

	0.000

 

CM-01               

	Exhaled VOC Trap 2  	144 h               

	17.6692 

	21.5887 

	3.9195 

	0.0478 

0.0472 	27.41

25.84	26.58

26.58	0.826

0.000	*

*	

	17.280

0.000	33.8651  

	0.000

 

CM-01               

	Exhaled VOC Trap 2  	168 h               

	17.7720 

	21.6849 

	3.9129 

	0.0477 

0.0484 	25.14

27.80	25.67

25.67	0.000

2.127	*

*	

	0.000

43.939	85.9652  

	0.000

 

CM-02               

	Exhaled VOC Trap 2  	  1 h               

	17.3715 

	25.1200 

	7.7485 

	0.0469 

0.0454 	35.90

36.32	25.67

25.67	10.234

10.654	

	*

*	218.204

234.664	1754.5228  

	0.003

 

CM-02               

	Exhaled VOC Trap 2  	  3 h               

	17.4032 

	25.1312 

	7.7280 

	0.0471 

0.0491 	39.92

40.17	25.67

25.67	14.254

14.504	

	*

*	302.627

295.392	2310.7471  

	0.004

 

CM-02               

	Exhaled VOC Trap 2  	  6 h               

	17.5781 

	25.3211 

	7.7430 

	0.0484 

0.0467 	48.46

43.98	25.67

25.67	22.794

18.314	

	*

*	470.945

392.157	3341.5019  

	0.006

 

CM-02               

	Exhaled VOC Trap 2  	 24 h               

	17.7019 

	25.4820 

	7.7801 

	0.0490 

0.0488 	14165.28

13924.75	25.67

25.67	14139.614

13899.084	

	

	288563.546

284817.290	2230480.1206  

	3.872

 

CM-02               

	Exhaled VOC Trap 2  	 48 h               

	17.6271 

	21.4378 

	3.8107 

	0.0475 

0.0490 	56.54

67.04	25.59

25.59	30.948

41.448	

	*

*	651.526

845.867	2853.0590  

	0.005

 

CM-02               

	Exhaled VOC Trap 2  	 72 h               

	17.6103 

	21.4186 

	3.8083 

	0.0478 

0.0488 	31.18

30.71	25.59

25.59	5.588

5.118	

	*

*	116.893

104.867	422.2645  

	0.001

 

CM-02               

	Exhaled VOC Trap 2  	 96 h               

	17.6750 

	21.5940 

	3.9190 

	0.0454 

0.0428 	32.99

27.39	26.58

26.58	6.406

0.806	

	*

*	141.101

18.832	313.3889  

	0.001

 

CM-02               

	Exhaled VOC Trap 2  	120 h               

	17.6740 

	21.5859 

	3.9119 

	0.0476 

0.0483 	25.36

30.32	26.58

26.58	0.000

3.736	*

*	

	0.000

77.350	151.2925  

	0.000

 

CM-02               

	Exhaled VOC Trap 2  	144 h               

	17.6951 

	21.6186 

	3.9235 

	0.0459 

0.0487 	33.24

28.52	26.58

26.58	6.656

1.936	

	*

*	145.011

39.754	362.4617  

	0.001

 

CM-02               

	Exhaled VOC Trap 2  

	168 h               

	17.6282 

	21.6312 

	4.0030 

	0.0458 

0.0488 	26.96

26.75	25.67

25.67	1.287

1.077	

	*

*	28.093

22.063	100.3872  

	0.000

 

Table 9 (contd).  Recovery of Radioactivity in VOC Trap 2 from Group C.

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-03               

	Exhaled VOC Trap 2  	  1 h               

	17.3866 

	25.1682 

	7.7816 

	0.0465 

0.0443 	35.47

36.14	25.67

25.67	9.804

10.474	

	*

*	210.833

236.428	1740.2035  

	0.003

 

CM-03               

	Exhaled VOC Trap 2  	  3 h               

	17.3954 

	25.1348 

	7.7394 

	0.0486 

0.0448 	41.02

39.29	25.67

25.67	15.354

13.624	

	*

*	315.921

304.102	2399.3005  

	0.004

 

CM-03               

	Exhaled VOC Trap 2  	  6 h               

	17.5554 

	25.3039 

	7.7485 

	0.0479 

0.0481 	41.73

46.66	25.67

25.67	16.064

20.994	

	*

*	335.360

436.460	2990.2261  

	0.005

 

CM-03               

	Exhaled VOC Trap 2  	 24 h               

	17.2213 

	24.9328 

	7.7115 

	0.0475 

0.0477 	27.57

25.34	28.57

28.57	0.000

0.000	*

*	

	0.000

0.000	0.0000  

	0.000

 

CM-03               

	Exhaled VOC Trap 2  	 48 h               

	17.6937 

	21.5069 

	3.8132 

	0.0477 

0.0476 	4014.48

3934.03	25.59

25.59	3988.888

3908.438	

	

	83624.476

82110.032	315989.4118  

	0.510

 

CM-03               

	Exhaled VOC Trap 2  	 72 h               

	17.7882 

	21.6101 

	3.8219 

	0.0475 

0.0495 	26.22

29.61	25.59

25.59	0.627

4.018	

	*

*	13.211

81.162	180.3404  

	0.000

 

CM-03               

	Exhaled VOC Trap 2  	 96 h               

	17.5522 

	21.4615 

	3.9093 

	0.0467 

0.0467 	25.79

26.04	26.58

26.58	0.000

0.000	*

*	

	0.000

0.000	0.0000  

	0.000

 

CM-03               

	Exhaled VOC Trap 2  	120 h               

	17.7909 

	21.6904 

	3.8995 

	0.0463 

0.0475 	26.48

25.16	26.58

26.58	0.000

0.000	*

*	

	0.000

0.000	0.0000  

	0.000

 

CM-03               

	Exhaled VOC Trap 2  	144 h               

	17.6494 

	21.5537 

	3.9043 

	0.0477 

0.0493 	26.48

24.69	26.58

26.58	0.000

0.000	*

*	

	0.000

0.000	0.0000  

	0.000

 

CM-03               

	Exhaled VOC Trap 2  	168 h               

	17.5559 

	21.4776 

	3.9217 

	0.0485 

0.0474 	22.91

30.93	25.67

25.67	0.000

5.257	*

*	

	0.000

110.900	217.4585  

	0.000

 



* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background. 

Table 10.  Recovery of Radioactivity in Nose Only Tube Rinse from Group
C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

CM-01               

	Nose Only Tube Rinse

Cage Rinse          

	  0 h               

168 h               

	227.64 

291.92 

	296.44 

563.41 

	68.80 

271.49 

	0.5421 

0.8379 

0.5657 0.5431 

0.4799 	951.59

1458.96

980.6976.81

71.62	0.92

0.92

0.9233.22

33.22	950.670

1458.040

979.77043.590

38.400	

	

*

*	1753.680

1740.112

1731.96080.261

80.017	119843.93

 

 21756.9550  

	0.217

 

 0.039

 

CM-02               

CM-02               

	Nose Only Tube Rinse

Cage Rinse          

	  0 h               

168 h               

	229.08 

290.04 

	334.99 

492.84 

	105.91 

202.80 

	0.5700 

0.5653 

0.5704 0.5662 

0.5789 	565.56

582.71

592.1093.38

100.62	0.92

0.92

0.9233.22

33.22	564.640

581.790

591.18060.160

67.400	

	

*

*	990.596

1029.170

1036.431106.252

116.428	107893.96

 

 22579.7434  

	0.187

 

 0.039

 

CM-03               

CM-03               

	Nose Only Tube Rinse

Cage Rinse          

	  0 h               

168 h               

	228.50 

290.11 

	347.05 

525.72 

	118.55 

235.61 

	0.5328 

0.5842 

0.5047 0.6135 

0.5854 	969.56

1072.25

923.5495.84

86.30	0.92

0.92

0.9233.22

33.22	968.640

1071.330

922.62062.620

53.080	

	

*

*	1818.018

1833.841

1828.056102.070

90.673	216547.99

 

 22706.1049  

	0.349

 

 0.037

 

CM-04               

CM-04               

	Nose Only Tube Rinse

Cage Rinse          

	  0 h               

168 h               

	228.72 

290.30 

	303.75 

588.24 

	75.03 

297.94 

	0.5872 

0.5935 

0.5891 0.5235 

0.6671 	714.90

701.06

738.8269.56

82.54	0.92

0.92

0.9233.22

33.22	713.980

700.140

737.90036.340

49.320	

	

*

*	1215.906

1179.680

1252.58969.417

73.932	91240.85

 

 21354.7493  

	0.596

 

 0.139

 



* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background.

Table 11.  Recovery of Radioactivity in Cage Rinse from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Alq wt	Orig DPM	Bkg DPM
Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Cage Rinse          

	168 h               

	291.92 

	563.41 

	271.49 

	0.5431 

0.4799 	76.81

71.62	33.22

33.22	43.590

38.400	

	*

*	80.261

80.017	21756.9550  

	0.039

 

CM-02               

	Cage Rinse          

	168 h               

	290.04 

	492.84 

	202.80 

	0.5662 

0.5789 	93.38

100.62	33.22

33.22	60.160

67.400	

	*

*	106.252

116.428	22579.7434  

	0.039

 

CM-03               

	Cage Rinse          

	168 h               

	290.11 

	525.72 

	235.61 

	0.6135 

0.5854 	95.84

86.30	33.22

33.22	62.620

53.080	

	*

*	102.070

90.673	22706.1049  

	0.037

 

CM-04               

	Cage Rinse          

	168 h               

	290.30 

	588.24 

	297.94 

	0.5235 

0.6671 	69.56

82.54	33.22

33.22	36.340

49.320	

	*

*	69.417

73.932	21354.7493  

	0.139

 

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background.

Table 14.  Recovery of Radioactivity in Carcass Digest from Group C.  

Subject	Sample	Time	Pot wt	Samp wt	Corr Samp	Homog wt	Corr Homog	Alq wt
Orig DPM	Bkg DPM	Calc DPM	LOD	LOQ	DPM/g	Sample DPM	Reco (%)

CM-01               

	Carcass Digest      

	168 h               

	108.43 

	298.32 

	189.89 

	743.25 

	634.82 

	0.9660 

0.7788 	2243.64

1783.77	2.02

2.02	2241.623

1781.753	

	

	2320.521

2287.819	1462733.1726 dpm

	2.649

 

CM-02               

	Carcass Digest      

	168 h               

	108.49 

	264.06 

	155.57 

	713.15 

	604.66 

	0.7983 

0.7838 	1639.65

1587.32	2.02

2.02	1637.633

1585.303	

	

	2051.401

2022.587	1231688.6221 dpm

	2.138

 

CM-03               

	Carcass Digest      

	168 h               

	108.50 

	321.55 

	213.05 

	764.55 

	656.05 

	0.8878 

0.7609 	2545.03

2140.18	2.02

2.02	2543.013

2138.163	

	

	2864.399

2810.045	1861359.4966 dpm

	3.003

 

CM-04               

	Carcass Digest      

	168 h               

	108.96 

	308.51 

	199.55 

	750.02 

	641.06 

	0.7264 

0.7493 	1645.23

1678.70	2.02

2.02	1643.213

1676.683	

	

	2262.133

2237.666	1442320.6245 dpm

	9.419

 

* in LOD column indicates that sample DPM were less than background DPM,
and in LOQ column indicates that sample DPM was less than 3 x
background.

Table 15.  Total Recovery of Radioactivity in Samples from Group C.  

Subject	Sample	Time	Sample DPM	Sample DPM Sum	Reco (%)

CM-01               	Urine               	  8 h               
1702841.2448 dpm	55226372.663 dpm	3.083

CM-01               	Urine               	 24 h               
1112436.2962 dpm

2.014

CM-01               	Urine               	 48 h               
152192.0689 dpm

0.276

CM-01               	Urine               	 72 h               
42766.6875 dpm

0.077

CM-01               	Urine               	 96 h               
20639.8664 dpm

0.037

CM-01               	Urine               	120 h               
13419.7170 dpm

0.024

CM-01               	Urine               	144 h               	7603.5986
dpm

0.014

CM-01               	Urine               	168 h               	6641.9187
dpm

0.012

CM-01               	Feces               	 24 h               
304280.7035 dpm

0.551

CM-01               	Feces               	 48 h               
81728.3597 dpm

0.148

CM-01               	Feces               	 72 h               
100278.6765 dpm

0.182

CM-01               	Feces               	 96 h               
33489.1935 dpm

0.061

CM-01               	Feces               	120 h               
20229.3497 dpm

0.037

CM-01               	Feces               	144 h               
23794.9089 dpm

0.043

CM-01               	Feces               	168 h               
15669.0866 dpm

0.028

CM-01               	Carcass Digest      	168 h               
1462733.1726 dpm

2.649

CM-01               	CO2 Trap 1          	  1 h               
246942.5678 dpm

0.447

CM-01               	CO2 Trap 1          	  3 h               	9585.5499
dpm

0.017

CM-01               	CO2 Trap 1          	  6 h               
1696930.6986 dpm

3.073

CM-01               	CO2 Trap 1          	 24 h               
6774444.4008 dpm

12.267

CM-01               	CO2 Trap 1          	 48 h               
464233.7551 dpm

0.841

CM-01               	CO2 Trap 1          	 72 h               
229702.9637 dpm

0.416

CM-01               	CO2 Trap 1          	 96 h               
102737.2420 dpm

0.186

CM-01               	CO2 Trap 1          	120 h               
82608.7736 dpm

0.150

CM-01               	CO2 Trap 1          	144 h               
55310.4673 dpm

0.100

CM-01               	CO2 Trap 1          	168 h               
37459.6609 dpm

0.068

CM-01               	CO2 Trap 2          	  1 h               	325.2943
dpm

0.001

CM-01               	CO2 Trap 2          	  3 h               
698451.4452 dpm

1.265

CM-01               	CO2 Trap 2          	  6 h               	7421.3663
dpm

0.013

CM-01               	CO2 Trap 2          	 24 h               
509232.8427 dpm

0.922

CM-01               	CO2 Trap 2          	 48 h               
114228.1428 dpm

0.207

CM-01               	CO2 Trap 2          	 72 h               
60433.0240 dpm

0.109

CM-01               	CO2 Trap 2          	 96 h               
32245.2092 dpm

0.058

CM-01               	CO2 Trap 2          	120 h               
21167.2592 dpm

0.038

CM-01               	CO2 Trap 2          	144 h               
22190.9255 dpm

0.040

CM-01               	CO2 Trap 2          	168 h               
18345.3295 dpm

0.033

CM-01               	Exhaled VOC Trap 1  	  1 h               
16241940.2899 dpm

29.410

CM-01               	Exhaled VOC Trap 1  	  3 h               
10063540.9441 dpm

18.222

CM-01               	Exhaled VOC Trap 1  	  6 h               
7162686.5449 dpm

12.970

CM-01               	Exhaled VOC Trap 1  	 24 h               
2267187.7811 dpm

4.105

CM-01               	Exhaled VOC Trap 1  	 48 h               
26940.0076 dpm

0.049

CM-01               	Exhaled VOC Trap 1  	 72 h               
10533.6467 dpm

0.019

CM-01               	Exhaled VOC Trap 1  	 96 h               	4981.5398
dpm

0.009

CM-01               	Exhaled VOC Trap 1  	120 h               	3418.5760
dpm

0.006

CM-01               	Exhaled VOC Trap 1  	144 h               	2555.5591
dpm

0.005

CM-01               	Exhaled VOC Trap 1  	168 h               	2092.2389
dpm

0.004

CM-01               	Exhaled VOC Trap 2  	  1 h               	965.4019
dpm

0.002

CM-01               	Exhaled VOC Trap 2  	  3 h               	1839.6735
dpm

0.003

CM-01               	Exhaled VOC Trap 2  	  6 h               	692.5500
dpm

0.001

CM-01               	Exhaled VOC Trap 2  	 24 h               
2996853.8999 dpm

5.426

CM-01               	Exhaled VOC Trap 2  	 48 h               	1766.0895
dpm

0.003

CM-01               	Exhaled VOC Trap 2  	 72 h               	376.9396
dpm

0.001

CM-01               	Exhaled VOC Trap 2  	 96 h               	353.7032
dpm

0.001

CM-01               	Exhaled VOC Trap 2  	120 h               	253.0892
dpm

0.000

CM-01               	Exhaled VOC Trap 2  	144 h               	33.8651
dpm

0.000

CM-01               	Exhaled VOC Trap 2  	168 h               	85.9652
dpm

0.000

CM-01               	Cage Rinse          	168 h               
21756.9550 dpm

0.039

CM-01               	Exposure Urine      	  0 h               	N.C.

 N.A.

CM-01               	Exposure Feces      	  0 h               
10931.7067 dpm

0.020

CM-01               	Nose Only Tube Rinse	  0 h               
119843.9291 dpm

0.217



Table 15 (contd).  Total Recovery of Radioactivity in Samples from Group
C.  

Subject	Sample	Time	Sample DPM	Sample DPM Sum	Reco (%)

CM-02               	Urine               	  8 h               
1724425.4933 dpm	57600304.435 dpm	2.994

CM-02               	Urine               	 24 h               
513448.6599 dpm

0.891

CM-02               	Urine               	 48 h               
99729.5573 dpm

0.173

CM-02               	Urine               	 72 h               
45884.1258 dpm

0.080

CM-02               	Urine               	 96 h               
25830.8763 dpm

0.045

CM-02               	Urine               	120 h               
13301.0590 dpm

0.023

CM-02               	Urine               	144 h               	8136.5127
dpm

0.014

CM-02               	Urine               	168 h               	8278.3864
dpm

0.014

CM-02               	Feces               	 24 h               
212846.8639 dpm

0.370

CM-02               	Feces               	 48 h               
106287.4716 dpm

0.185

CM-02               	Feces               	 72 h               
72685.7237 dpm

0.126

CM-02               	Feces               	 96 h               
28211.6997 dpm

0.049

CM-02               	Feces               	120 h               
30004.6363 dpm

0.052

CM-02               	Feces               	144 h               
19753.2879 dpm

0.034

CM-02               	Feces               	168 h               
19853.2934 dpm

0.034

CM-02               	Carcass Digest      	168 h               
1231688.6221 dpm

2.138

CM-02               	CO2 Trap 1          	  1 h               
239877.4440 dpm

0.416

CM-02               	CO2 Trap 1          	  3 h               
680035.5272 dpm

1.181

CM-02               	CO2 Trap 1          	  6 h               
2064541.3872 dpm

3.584

CM-02               	CO2 Trap 1          	 24 h               
6471455.9649 dpm

11.235

CM-02               	CO2 Trap 1          	 48 h               
354163.2880 dpm

0.615

CM-02               	CO2 Trap 1          	 72 h               
139928.4295 dpm

0.243

CM-02               	CO2 Trap 1          	 96 h               
85187.3860 dpm

0.148

CM-02               	CO2 Trap 1          	120 h               
60304.5536 dpm

0.105

CM-02               	CO2 Trap 1          	144 h               
57990.6625 dpm

0.101

CM-02               	CO2 Trap 1          	168 h               
37901.8063 dpm

0.066

CM-02               	CO2 Trap 2          	  1 h               	1228.6300
dpm

0.002

CM-02               	CO2 Trap 2          	  3 h               	6468.1692
dpm

0.011

CM-02               	CO2 Trap 2          	  6 h               
12449.4979 dpm

0.022

CM-02               	CO2 Trap 2          	 24 h               
323859.8783 dpm

0.562

CM-02               	CO2 Trap 2          	 48 h               
131217.5367 dpm

0.228

CM-02               	CO2 Trap 2          	 72 h               
78774.4871 dpm

0.137

CM-02               	CO2 Trap 2          	 96 h               
44309.3432 dpm

0.077

CM-02               	CO2 Trap 2          	120 h               
38785.5875 dpm

0.067

CM-02               	CO2 Trap 2          	144 h               
21421.1500 dpm

0.037

CM-02               	CO2 Trap 2          	168 h               
16709.1902 dpm

0.029

CM-02               	Exhaled VOC Trap 1  	  1 h               
19776671.7311 dpm

34.334

CM-02               	Exhaled VOC Trap 1  	  3 h               
12141553.0411 dpm

21.079

CM-02               	Exhaled VOC Trap 1  	  6 h               
7333740.3866 dpm

12.732

CM-02               	Exhaled VOC Trap 1  	 24 h               
699718.1910 dpm

1.215

CM-02               	Exhaled VOC Trap 1  	 48 h               
20939.6603 dpm

0.036

CM-02               	Exhaled VOC Trap 1  	 72 h               
14866.8688 dpm

0.026

CM-02               	Exhaled VOC Trap 1  	 96 h               
10938.1387 dpm

0.019

CM-02               	Exhaled VOC Trap 1  	120 h               	5960.0466
dpm

0.010

CM-02               	Exhaled VOC Trap 1  	144 h               	4682.9841
dpm

0.008

CM-02               	Exhaled VOC Trap 1  	168 h               	3402.8124
dpm

0.006

CM-02               	Exhaled VOC Trap 2  	  1 h               	1754.5228
dpm

0.003

CM-02               	Exhaled VOC Trap 2  	  3 h               	2310.7471
dpm

0.004

CM-02               	Exhaled VOC Trap 2  	  6 h               	3341.5019
dpm

0.006

CM-02               	Exhaled VOC Trap 2  	 24 h               
2230480.1206 dpm

3.872

CM-02               	Exhaled VOC Trap 2  	 48 h               	2853.0590
dpm

0.005

CM-02               	Exhaled VOC Trap 2  	 72 h               	422.2645
dpm

0.001

CM-02               	Exhaled VOC Trap 2  	 96 h               	313.3889
dpm

0.001

CM-02               	Exhaled VOC Trap 2  	120 h               	151.2925
dpm

0.000

CM-02               	Exhaled VOC Trap 2  	144 h               	362.4617
dpm

0.001

CM-02               	Exhaled VOC Trap 2  	168 h               	100.3872
dpm

0.000

CM-02               	Blood               	168 h               	772.7276
dpm

0.001

CM-02               	Spleen              	168 h               	2713.8934
dpm

0.005

Table 15 (contd).  Total Recovery of Radioactivity in Samples from
Group C.  

CM-02               	Liver               	168 h               
68605.0539 dpm

0.119

CM-02               	Kidney              	168 h               
14078.4226 dpm

0.024

CM-02               	Brain               	168 h               	8225.5161
dpm

0.014

CM-02               	Heart               	168 h               	3921.6704
dpm

0.007

CM-02               	Lung                	168 h               	7171.9886
dpm

0.012

CM-02               	Stomach             	168 h               	6507.6618
dpm

0.011

CM-02               	Small Intestine     	168 h               
15092.2206 dpm

0.026

CM-02               	Femur               	168 h               	3312.0956
dpm

0.006

CM-02               	Testes              	168 h               
14999.9728 dpm

0.026

CM-02               	Cecum+Lg Int+Rect   	168 h               
10720.4814 dpm

0.019

CM-02               	Adip (Abdominal)    	168 h               	3212.4929
dpm

0.006

CM-02               	Cage Rinse          	168 h               
22579.7434 dpm

0.039

CM-02               	Skin (Neck)         	168 h               	2992.3947
dpm

0.005

CM-02               	Adipose (subcut)    	168 h               	3668.5436
dpm

0.006

CM-02               	Stomach Contents    	168 h               	604.4376
dpm

0.001

CM-02               	Muscle Gastrocnemius	168 h               	2454.9885
dpm

0.004

CM-02               	Small Intestine Cont	168 h               
10854.0784 dpm

0.019

CM-02               	Lg Int + Cecum Cont 	168 h               	8382.2992
dpm

0.015

CM-02               	Exposure Urine      	  0 h               	N.C.

 N.A.

CM-02               	Exposure Feces      	  0 h               	N.C.

 N.A.

CM-02               	Nose Only Tube Rinse	  0 h               
107893.9562 dpm

0.187



Table 15 (contd).  Total Recovery of Radioactivity in Samples from
Group C.  

Subject	Sample	Time	Sample DPM	Sample DPM Sum	Reco (%)

CM-03               	Urine               	  8 h               
1830907.9353 dpm	61974739.573 dpm	2.954

CM-03               	Urine               	 24 h               
1035036.8761 dpm

1.670

CM-03               	Urine               	 48 h               
94140.8610 dpm

0.152

CM-03               	Urine               	 72 h               
36422.3233 dpm

0.059

CM-03               	Urine               	 96 h               
21467.4863 dpm

0.035

CM-03               	Urine               	120 h               
12046.4569 dpm

0.019

CM-03               	Urine               	144 h               
11128.9383 dpm

0.018

CM-03               	Urine               	168 h               	6406.4016
dpm

0.010

CM-03               	Feces               	 24 h               
526783.7049 dpm

0.850

CM-03               	Feces               	 48 h               
153155.1821 dpm

0.247

CM-03               	Feces               	 72 h               
53383.2190 dpm

0.086

CM-03               	Feces               	 96 h               
80773.0200 dpm

0.130

CM-03               	Feces               	120 h               
30611.1993 dpm

0.049

CM-03               	Feces               	144 h               	7816.8261
dpm

0.013

CM-03               	Feces               	168 h               
38406.6001 dpm

0.062

CM-03               	Carcass Digest      	168 h               
1861359.4966 dpm

3.003

CM-03               	CO2 Trap 1          	  1 h               
236323.1407 dpm

0.381

CM-03               	CO2 Trap 1          	  3 h               
666619.0295 dpm

1.076

CM-03               	CO2 Trap 1          	  6 h               
2227004.5358 dpm

3.593

CM-03               	CO2 Trap 1          	 24 h               
7612540.0951 dpm

12.283

CM-03               	CO2 Trap 1          	 48 h               
739592.7459 dpm

1.193

CM-03               	CO2 Trap 1          	 72 h               
247644.9995 dpm

0.400

CM-03               	CO2 Trap 1          	 96 h               
127633.4003 dpm

0.206

CM-03               	CO2 Trap 1          	120 h               
112926.1187 dpm

0.182

CM-03               	CO2 Trap 1          	144 h               
90463.3291 dpm

0.146

CM-03               	CO2 Trap 1          	168 h               
52132.9559 dpm

0.084

CM-03               	CO2 Trap 2          	  1 h               	1179.8598
dpm

0.002

CM-03               	CO2 Trap 2          	  3 h               	5537.2663
dpm

0.009

CM-03               	CO2 Trap 2          	  6 h               
16930.4947 dpm

0.027

CM-03               	CO2 Trap 2          	 24 h               
776560.8440 dpm

1.253

CM-03               	CO2 Trap 2          	 48 h               
258008.2599 dpm

0.416

CM-03               	CO2 Trap 2          	 72 h               
82975.0407 dpm

0.134

CM-03               	CO2 Trap 2          	 96 h               
42802.4303 dpm

0.069

CM-03               	CO2 Trap 2          	120 h               
22766.1409 dpm

0.037

CM-03               	CO2 Trap 2          	144 h               
27059.2818 dpm

0.044

CM-03               	CO2 Trap 2          	168 h               
22151.0729 dpm

0.036

CM-03               	Exhaled VOC Trap 1  	  1 h               
17677062.8099 dpm

28.523

CM-03               	Exhaled VOC Trap 1  	  3 h               
12285157.3812 dpm

19.823

CM-03               	Exhaled VOC Trap 1  	  6 h               
8642869.2691 dpm

13.946

CM-03               	Exhaled VOC Trap 1  	 24 h               
3497576.8167 dpm

5.644

CM-03               	Exhaled VOC Trap 1  	 48 h               
41378.3150 dpm

0.067

CM-03               	Exhaled VOC Trap 1  	 72 h               
11344.6259 dpm

0.018

CM-03               	Exhaled VOC Trap 1  	 96 h               	6050.3966
dpm

0.010

CM-03               	Exhaled VOC Trap 1  	120 h               	3879.1408
dpm

0.006

CM-03               	Exhaled VOC Trap 1  	144 h               	2865.3259
dpm

0.005

CM-03               	Exhaled VOC Trap 1  	168 h               	2426.5659
dpm

0.004

CM-03               	Exhaled VOC Trap 2  	  1 h               	1740.2035
dpm

0.003

CM-03               	Exhaled VOC Trap 2  	  3 h               	2399.3005
dpm

0.004

CM-03               	Exhaled VOC Trap 2  	  6 h               	2990.2261
dpm

0.005

CM-03               	Exhaled VOC Trap 2  	 24 h               	0.0000
dpm

0.000

CM-03               	Exhaled VOC Trap 2  	 48 h               
315989.4118 dpm

0.510

CM-03               	Exhaled VOC Trap 2  	 72 h               	180.3404
dpm

0.000

CM-03               	Exhaled VOC Trap 2  	 96 h               	0.0000
dpm

0.000

CM-03               	Exhaled VOC Trap 2  	120 h               	0.0000
dpm

0.000

CM-03               	Exhaled VOC Trap 2  	144 h               	0.0000
dpm

0.000

CM-03               	Exhaled VOC Trap 2  	168 h               	217.4585
dpm

0.000

CM-03               	Cage Rinse          	168 h               
22706.1049 dpm

0.037

CM-03               	Exposure Urine      	  0 h               	N.C.

 N.A.

CM-03               	Exposure Feces      	  0 h               
72660.3202 dpm

0.117

CM-03               	Nose Only Tube Rinse	  0 h               
216547.9918 dpm

0.349



Table 15 (contd).  Total Recovery of Radioactivity in Samples from
Group C.  

Subject	Sample	Time	Sample DPM	Sample DPM Sum	Reco (%)

CM-04               	Urine               	  8 h               
989422.8048 dpm	15313501.108 dpm	6.461

CM-04               	Urine               	 24 h               
1337202.8125 dpm

8.732

CM-04               	Urine               	 48 h               
183682.3569 dpm

1.199

CM-04               	Urine               	 72 h               
39186.3623 dpm

0.256

CM-04               	Urine               	 96 h               
13567.7919 dpm

0.089

CM-04               	Urine               	120 h               
11819.8278 dpm

0.077

CM-04               	Urine               	144 h               	9219.9960
dpm

0.060

CM-04               	Urine               	168 h               	7059.9188
dpm

0.046

CM-04               	Feces               	 24 h               
284923.2872 dpm

1.861

CM-04               	Feces               	 48 h               
108474.3403 dpm

0.708

CM-04               	Feces               	 72 h               
43780.5359 dpm

0.286

CM-04               	Feces               	 96 h               
61476.9369 dpm

0.401

CM-04               	Feces               	120 h               
23743.7041 dpm

0.155

CM-04               	Feces               	144 h               
18835.1115 dpm

0.123

CM-04               	Feces               	168 h               
16712.6327 dpm

0.109

CM-04               	Carcass Digest      	168 h               
1442320.6245 dpm

9.419

CM-04               	CO2 Trap 1          	  1 h               
244957.6956 dpm

1.600

CM-04               	CO2 Trap 1          	  3 h               
722853.7853 dpm

4.720

CM-04               	CO2 Trap 1          	  6 h               
1734658.5733 dpm

11.328

CM-04               	CO2 Trap 1          	 24 h               
6059912.7649 dpm

39.572

CM-04               	CO2 Trap 1          	 48 h               
392843.3036 dpm

2.565

CM-04               	CO2 Trap 1          	 72 h               
186883.0429 dpm

1.220

CM-04               	CO2 Trap 1          	 96 h               
116115.8257 dpm

0.758

CM-04               	CO2 Trap 1          	120 h               
82913.4703 dpm

0.541

CM-04               	CO2 Trap 1          	144 h               
62329.0532 dpm

0.407

CM-04               	CO2 Trap 1          	168 h               
40464.7951 dpm

0.264

CM-04               	CO2 Trap 2          	  1 h               	224.0153
dpm

0.001

CM-04               	CO2 Trap 2          	  3 h               	2323.2219
dpm

0.015

CM-04               	CO2 Trap 2          	  6 h               
11512.7544 dpm

0.075

CM-04               	CO2 Trap 2          	 24 h               
631742.0214 dpm

4.125

CM-04               	CO2 Trap 2          	 48 h               
144632.5680 dpm

0.944

CM-04               	CO2 Trap 2          	 72 h               
68123.3236 dpm

0.445

CM-04               	CO2 Trap 2          	 96 h               
35297.7887 dpm

0.231

CM-04               	CO2 Trap 2          	120 h               
24766.1932 dpm

0.162

CM-04               	CO2 Trap 2          	144 h               
18352.8805 dpm

0.120

CM-04               	CO2 Trap 2          	168 h               
15180.6258 dpm

0.099

CM-04               	Exhaled VOC Trap 1  	  1 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	  3 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	  6 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	 24 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	 48 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	 72 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	 96 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	120 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	144 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 1  	168 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	  1 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	  3 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	  6 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	 24 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	 48 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	 72 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	 96 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	120 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	144 h               	N.C.

 N.A.

CM-04               	Exhaled VOC Trap 2  	168 h               	N.C.

 N.A.

CM-04               	Cage Rinse          	168 h               
21354.7493 dpm

0.139

CM-04               	Exposure Urine      	  0 h               	N.C.

 N.A.

CM-04               	Exposure Feces      	  0 h               
13388.7664 dpm

0.087

CM-04               	Nose Only Tube Rinse	  0 h               
91240.8456 dpm

0.596





Appendix I

Blood Sample Collection and Analysis for DIPE, Acetone and Isopropanol
Table 1.  Blood Sample Collection Times.

Subject	Sample	Dose Time	Nominal 

Time	Elapsed Time 

(hh:mm:ss)	Capture Time







	AM-01	Blood	No Dose	Predose	NA	9/27/2007 8:42:04 AM

AM-02	Blood	No Dose	Predose	NA	9/27/2007 8:46:04 AM

AM-03	Blood	No Dose	Predose	NA	9/27/2007 8:51:53 AM

AM-04	Blood	No Dose	Predose	NA	9/27/2007 8:56:58 AM

AM-05	Blood	No Dose	Predose	NA	9/27/2007 9:01:48 AM

AM-06	Blood	No Dose	Predose	NA	9/27/2007 9:06:53 AM

AM-07	Blood	No Dose	Predose	NA	9/27/2007 9:43:54 AM

AM-08	Blood	No Dose	Predose	NA	9/27/2007 9:49:50 AM

AF-01	Blood	No Dose	Predose	NA	9/27/2007 9:10:32 AM

AF-02	Blood	No Dose	Predose	NA	9/27/2007 9:17:04 AM

AF-03	Blood	No Dose	Predose	NA	9/27/2007 9:22:33 AM

AF-04	Blood	No Dose	Predose	NA	9/27/2007 9:27:41 AM

AF-05	Blood	No Dose	Predose	NA	9/27/2007 9:32:50 AM

AF-06	Blood	No Dose	Predose	NA	9/27/2007 9:37:48 AM

AF-07	Blood	No Dose	Predose	NA	9/27/2007 9:54:48 AM

AF-08	Blood	No Dose	Predose	NA	9/27/2007 10:00:43 AM

AM-01	Blood	9/27/2007 9:45:07 AM	5 m	0 h  5 m  11 s	9/27/2007 9:50:18 AM

AM-01	Blood	9/27/2007 9:45:07 AM	15 m	0 h  15 m  26 s	9/27/2007 10:00:33
AM

AM-01	Blood	9/27/2007 9:45:07 AM	1 h	1 h  4 m  29 s	9/27/2007 10:49:36
AM

AM-02	Blood	9/27/2007 9:49:10 AM	5 m	0 h  4 m  47 s	9/27/2007 9:53:57 AM

AM-02	Blood	9/27/2007 9:49:10 AM	15 m	0 h  15 m  16 s	9/27/2007 10:04:26
AM

AM-02	Blood	9/27/2007 9:49:10 AM	1 h	1 h  0 m  29 s	9/27/2007 10:49:39
AM

AM-03	Blood	9/27/2007 9:53:01 AM	5 m	0 h  5 m  43 s	9/27/2007 9:58:44 AM

AM-03	Blood	9/27/2007 9:53:01 AM	15 m	0 h  15 m  12 s	9/27/2007 10:08:13
AM

AM-03	Blood	9/27/2007 9:53:01 AM	1 h	0 h  59 m  58 s	9/27/2007 10:52:59
AM

AM-04	Blood	9/27/2007 9:59:24 AM	10 m	0 h  10 m  25 s	9/27/2007 10:09:49
AM

AM-04	Blood	9/27/2007 9:59:24 AM	30 m	0 h  29 m  29 s	9/27/2007 10:28:53
AM

AM-04	Blood	9/27/2007 9:59:24 AM	2 h	2 h  0 m  13 s	9/27/2007 11:59:37
AM

AM-05	Blood	9/27/2007 10:05:57 AM	10 m	0 h  9 m  33 s	9/27/2007 10:15:30
AM

AM-05	Blood	9/27/2007 10:05:57 AM	30 m	0 h  29 m  1 s	9/27/2007 10:34:58
AM

AM-05	Blood	9/27/2007 10:05:57 AM	2 h	2 h  0 m  30 s	9/27/2007 12:06:27
PM

AM-06	Blood	9/27/2007 10:10:12 AM	10 m	0 h  10 m  14 s	9/27/2007
10:20:26 AM

AM-06	Blood	9/27/2007 10:10:12 AM	30 m	0 h  29 m  56 s	9/27/2007
10:40:08 AM

AM-06	Blood	9/27/2007 10:10:12 AM	2 h	2 h  0 m  2 s	9/27/2007 12:10:14
PM



Table 1 (continued).  Blood Sample Collection Times.

Subject	Sample	Dose Time	Nominal 

Time	Elapsed Time 

(hh:mm:ss)	Capture Time







	AF-01	Blood	9/27/2007 10:14:32 AM	5 m	0 h  4 m  40 s	9/27/2007 10:19:12
AM

AF-01	Blood	9/27/2007 10:14:32 AM	15 m	0 h  14 m  30 s	9/27/2007
10:29:02 AM

AF-01	Blood	9/27/2007 10:14:32 AM	1 h	0 h  59 m  33 s	9/27/2007 11:14:05
AM

AF-02	Blood	9/27/2007 10:19:07 AM	5 m	0 h  5 m  3 s	9/27/2007 10:24:10
AM

AF-02	Blood	9/27/2007 10:19:07 AM	15 m	0 h  15 m  11 s	9/27/2007
10:34:18 AM

AF-02	Blood	9/27/2007 10:19:07 AM	1 h	1 h  0 m  0 s	9/27/2007 11:19:07
AM

AF-03	Blood	9/27/2007 10:24:59 AM	5 m	0 h  3 m  56 s	9/27/2007 10:28:55
AM

AF-03	Blood	9/27/2007 10:24:59 AM	15 m	0 h  13 m  53 s	9/27/2007
10:38:52 AM

AF-03	Blood	9/27/2007 10:24:59 AM	1 h	1 h  0 m  11 s	9/27/2007 11:25:10
AM

AF-04	Blood	9/27/2007 10:30:31 AM	10 m	0 h  9 m  37 s	9/27/2007 10:40:08
AM

AF-04	Blood	9/27/2007 10:30:31 AM	30 m	0 h  29 m  41 s	9/27/2007
11:00:12 AM

AF-04	Blood	9/27/2007 10:30:31 AM	2 h	2 h  0 m  38 s	9/27/2007 12:31:09
PM

AF-05	Blood	9/27/2007 10:35:13 AM	10 m	0 h  10 m  11 s	9/27/2007
10:45:24 AM

AF-05	Blood	9/27/2007 10:35:13 AM	30 m	0 h  29 m  46 s	9/27/2007
11:04:59 AM

AF-05	Blood	9/27/2007 10:35:13 AM	2 h	2 h  1 m  19 s	9/27/2007 12:36:32
PM

AF-06	Blood	9/27/2007 10:40:17 AM	10 m	0 h  9 m  45 s	9/27/2007 10:50:02
AM

AF-06	Blood	9/27/2007 10:40:17 AM	30 m	0 h  30 m  17 s	9/27/2007
11:10:34 AM

AF-06	Blood	9/27/2007 10:40:17 AM	2 h	2 h  0 m  12 s	9/27/2007 12:40:29
PM

AM-01	Blood	9/27/2007 9:45:07 AM	4 h	4 h  1 m  20 s	9/27/2007 1:46:27 PM

AM-02	Blood	9/27/2007 9:49:10 AM	4 h	3 h  59 m  55 s	9/27/2007 1:49:05
PM

AM-03	Blood	9/27/2007 9:53:01 AM	4 h	4 h  1 m  22 s	9/27/2007 1:54:23 PM

AF-01	Blood	9/27/2007 10:14:32 AM	4 h	4 h  0 m  11 s	9/27/2007 2:14:43
PM

AF-02	Blood	9/27/2007 10:19:07 AM	4 h	4 h  0 m  15 s	9/27/2007 2:19:22
PM

AF-03	Blood	9/27/2007 10:24:59 AM	4 h	3 h  59 m  39 s	9/27/2007 2:24:38
PM

AM-01	Blood	9/27/2007 9:45:07 AM	6.25 h	6 h  15 m  21 s	9/27/2007
4:00:28 PM

AM-01	Blood	9/27/2007 9:45:07 AM	7 h	7 h  0 m  4 s	9/27/2007 4:45:11 PM

AM-01	Blood	9/27/2007 9:45:07 AM	8 h	8 h  0 m  48 s	9/27/2007 5:45:55 PM

AM-02	Blood	9/27/2007 9:49:10 AM	6.25 h	6 h  15 m  14 s	9/27/2007
4:04:24 PM

AM-02	Blood	9/27/2007 9:49:10 AM	7 h	6 h  59 m  54 s	9/27/2007 4:49:04
PM

AM-02	Blood	9/27/2007 9:49:10 AM	8 h	8 h  0 m  2 s	9/27/2007 5:49:12 PM

AM-03	Blood	9/27/2007 9:53:01 AM	6.25 h	6 h  14 m  53 s	9/27/2007
4:07:54 PM

AM-03	Blood	9/27/2007 9:53:01 AM	7 h	6 h  59 m  57 s	9/27/2007 4:52:58
PM

AM-03	Blood	9/27/2007 9:53:01 AM	8 h	8 h  0 m  2 s	9/27/2007 5:53:03 PM

AM-04	Blood	9/27/2007 9:59:24 AM	6 h	6 h  0 m  41 s	9/27/2007 4:00:05 PM

AM-04	Blood	9/27/2007 9:59:24 AM	6.50 h	6 h  29 m  59 s	9/27/2007
4:29:23 PM

AM-04	Blood	9/27/2007 9:59:24 AM	7.33 h	7 h  18 m  37 s	9/27/2007
5:18:01 PM

AM-05	Blood	9/27/2007 10:05:57 AM	6 h	6 h  3 m  19 s	9/27/2007 4:09:16
PM

AM-05	Blood	9/27/2007 10:05:57 AM	6.50 h	6 h  31 m  31 s	9/27/2007
4:37:28 PM

AM-05	Blood	9/27/2007 10:05:57 AM	7.33 h	7 h  18 m  8 s	9/27/2007
5:24:05 PM

AM-06	Blood	9/27/2007 10:10:12 AM	6 h	6 h  0 m  42 s	9/27/2007 4:10:54
PM

AM-06	Blood	9/27/2007 10:10:12 AM	6.50 h	6 h  30 m  40 s	9/27/2007
4:40:52 PM

Table 1 (continued).  Blood Sample Collection Times.

Subject	Sample	Dose Time	Nominal 

Time	Elapsed Time 

(hh:mm:ss)	Capture Time







	AM-06	Blood	9/27/2007 10:10:12 AM	7.33 h	7 h  18 m  33 s	9/27/2007
5:28:45 PM

AF-01	Blood	9/27/2007 10:14:32 AM	6.25 h	6 h  15 m  14 s	9/27/2007
4:29:46 PM

AF-01	Blood	9/27/2007 10:14:32 AM	7 h	7 h  0 m  24 s	9/27/2007 5:14:56
PM

AF-01	Blood	9/27/2007 10:14:32 AM	8 h	7 h  59 m  38 s	9/27/2007 6:14:10
PM

AF-02	Blood	9/27/2007 10:19:07 AM	6.25 h	6 h  14 m  44 s	9/27/2007
4:33:51 PM

AF-02	Blood	9/27/2007 10:19:07 AM	7 h	6 h  59 m  58 s	9/27/2007 5:19:05
PM

AF-02	Blood	9/27/2007 10:19:07 AM	8 h	7 h  59 m  39 s	9/27/2007 6:18:46
PM

AF-03	Blood	9/27/2007 10:24:59 AM	6.25 h	6 h  15 m  3 s	9/27/2007
4:40:02 PM

AF-03	Blood	9/27/2007 10:24:59 AM	7 h	6 h  59 m  42 s	9/27/2007 5:24:41
PM

AF-03	Blood	9/27/2007 10:24:59 AM	8 h	7 h  59 m  39 s	9/27/2007 6:24:38
PM

AF-04	Blood	9/27/2007 10:30:31 AM	6 h	6 h  0 m  38 s	9/27/2007 4:31:09
PM

AF-04	Blood	9/27/2007 10:30:31 AM	6.50 h	6 h  29 m  5 s	9/27/2007
4:59:36 PM

AF-04	Blood	9/27/2007 10:30:31 AM	7.33 h	7 h  18 m  42 s	9/27/2007
5:49:13 PM

AF-05	Blood	9/27/2007 10:35:13 AM	6 h	6 h  0 m  15 s	9/27/2007 4:35:28
PM

AF-05	Blood	9/27/2007 10:35:13 AM	6.50 h	6 h  29 m  44 s	9/27/2007
5:04:57 PM

AF-05	Blood	9/27/2007 10:35:13 AM	7.33 h	7 h  19 m  1 s	9/27/2007
5:54:14 PM

AF-06	Blood	9/27/2007 10:40:17 AM	6 h	6 h  3 m  36 s	9/27/2007 4:43:53
PM

AF-06	Blood	9/27/2007 10:40:17 AM	6.50 h	6 h  29 m  43 s	9/27/2007
5:10:00 PM

AF-06	Blood	9/27/2007 10:40:17 AM	7.33 h	7 h  19 m  6 s	9/27/2007
5:59:23 PM

AM-04	Blood	9/27/2007 9:59:24 AM	10 h	9 h  59 m  34 s	9/27/2007 7:58:58
PM

AM-05	Blood	9/27/2007 10:05:57 AM	10 h	9 h  59 m  56 s	9/27/2007 8:05:53
PM

AM-06	Blood	9/27/2007 10:10:12 AM	10 h	9 h  59 m  34 s	9/27/2007 8:09:46
PM

AF-04	Blood	9/27/2007 10:30:31 AM	10 h	10 h  0 m  8 s	9/27/2007 8:30:39
PM

AF-05	Blood	9/27/2007 10:35:13 AM	10 h	9 h  59 m  43 s	9/27/2007 8:34:56
PM

AF-06	Blood	9/27/2007 10:40:17 AM	10 h	9 h  59 m  51 s	9/27/2007 8:40:08
PM

AM-01	Blood	9/27/2007 9:45:07 AM	16 h	15 h  59 m  58 s	9/28/2007 1:45:05
AM

AM-02	Blood	9/27/2007 9:49:10 AM	16 h	16 h  0 m  17 s	9/28/2007 1:49:27
AM

AM-03	Blood	9/27/2007 9:53:01 AM	16 h	15 h  59 m  50 s	9/28/2007 1:52:51
AM

AF-01	Blood	9/27/2007 10:14:32 AM	16 h	15 h  59 m  33 s	9/28/2007
2:14:05 AM

AF-02	Blood	9/27/2007 10:19:07 AM	16 h	16 h  0 m  22 s	9/28/2007 2:19:29
AM

AF-03	Blood	9/27/2007 10:24:59 AM	16 h	16 h  0 m  38 s	9/28/2007 2:25:37
AM

AM-04	Blood	9/27/2007 9:59:24 AM	24 h	23 h  59 m  17 s	9/28/2007 9:58:41
AM

AM-05	Blood	9/27/2007 10:05:57 AM	24 h	23 h  59 m  47 s	9/28/2007
10:05:44 AM

AM-06	Blood	9/27/2007 10:10:12 AM	24 h	24 h  1 m  47 s	9/28/2007
10:11:59 AM

AF-04	Blood	9/27/2007 10:30:31 AM	24 h	23 h  59 m  25 s	9/28/2007
10:29:56 AM

AF-05	Blood	9/27/2007 10:35:13 AM	24 h	24 h  0 m  52 s	9/28/2007
10:36:05 AM

AF-06	Blood	9/27/2007 10:40:17 AM	24 h	23 h  59 m  37 s	9/28/2007
10:39:54 AM





Table 2.  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AM-01               	Blood               	Predose	11.4071 g	11.5786 g
0.1715 g

AM-01               	Blood               	5 m	11.3700 g	11.5151 g	0.1451
g

AM-01               	Blood               	10 m	N.C.	N.C.	N.C.

AM-01               	Blood               	15 m	11.1686 g	11.3501 g
0.1815 g

AM-01               	Blood               	30 m	N.C.	N.C.	N.C.

AM-01               	Blood               	1 h	11.3947 g	11.5830 g	0.1883
g

AM-01               	Blood               	2 h	N.C.	N.C.	N.C.

AM-01               	Blood               	4 h	11.2188 g	11.4168 g	0.1980
g

AM-01               	Blood               	6 h	N.C.	N.C.	N.C.

AM-01               	Blood               	6.25 h	11.3839 g	11.5485 g
0.1646 g

AM-01               	Blood               	6.50 h	N.C.	N.C.	N.C.

AM-01               	Blood               	7 h	11.3850 g	11.5548 g	0.1698
g

AM-01               	Blood               	7.33 h	N.C.	N.C.	N.C.

AM-01               	Blood               	8 h	11.3953 g	11.5450 g	0.1497
g

AM-01               	Blood               	10 h	N.C.	N.C.	N.C.

AM-01               	Blood               	16 h	11.5298 g	11.6900 g
0.1602 g

AM-01               	Blood               	24 h	N.C.	N.C.	N.C.

AM-02               	Blood               	Predose	11.2103 g	11.3715 g
0.1612 g

AM-02               	Blood               	5 m	11.1642 g	11.3751 g	0.2109
g

AM-02               	Blood               	10 m	N.C.	N.C.	N.C.

AM-02               	Blood               	15 m	11.3748 g	11.5851 g
0.2103 g

AM-02               	Blood               	30 m	N.C.	N.C.	N.C.

AM-02               	Blood               	1 h	11.1905 g	11.4920 g	0.3015
g

AM-02               	Blood               	2 h	N.C.	N.C.	N.C.

AM-02               	Blood               	4 h	11.2054 g	11.3703 g	0.1649
g

AM-02               	Blood               	6 h	N.C.	N.C.	N.C.

AM-02               	Blood               	6.25 h	11.4053 g	11.5638 g
0.1585 g

AM-02               	Blood               	6.50 h	N.C.	N.C.	N.C.

AM-02               	Blood               	7 h	11.1948 g	11.3717 g	0.1769
g

AM-02               	Blood               	7.33 h	N.C.	N.C.	N.C.

AM-02               	Blood               	8 h	11.2456 g	11.3945 g	0.1489
g

AM-02               	Blood               	10 h	N.C.	N.C.	N.C.

AM-02               	Blood               	16 h	11.2549 g	11.4349 g
0.1800 g

AM-02               	Blood               	24 h	N.C.	N.C.	N.C.



Table 2 (contd).  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AM-03               	Blood               	Predose	11.3612 g	11.5564 g
0.1952 g

AM-03               	Blood               	5 m	11.1794 g	11.3504 g	0.1710
g

AM-03               	Blood               	10 m	N.C.	N.C.	N.C.

AM-03               	Blood               	15 m	11.3676 g	11.5785 g
0.2109 g

AM-03               	Blood               	30 m	N.C.	N.C.	N.C.

AM-03               	Blood               	1 h	11.1694 g	11.3862 g	0.2168
g

AM-03               	Blood               	2 h	N.C.	N.C.	N.C.

AM-03               	Blood               	4 h	11.2131 g	11.4204 g	0.2073
g

AM-03               	Blood               	6 h	N.C.	N.C.	N.C.

AM-03               	Blood               	6.25 h	11.1978 g	11.3562 g
0.1584 g

AM-03               	Blood               	6.50 h	N.C.	N.C.	N.C.

AM-03               	Blood               	7 h	11.3806 g	11.5546 g	0.1740
g

AM-03               	Blood               	7.33 h	N.C.	N.C.	N.C.

AM-03               	Blood               	8 h	11.2156 g	11.3954 g	0.1798
g

AM-03               	Blood               	10 h	N.C.	N.C.	N.C.

AM-03               	Blood               	16 h	11.1806 g	11.3376 g
0.1570 g

AM-03               	Blood               	24 h	N.C.	N.C.	N.C.

AM-04               	Blood               	Predose	11.3950 g	11.5575 g
0.1625 g

AM-04               	Blood               	5 m	N.C.	N.C.	N.C.

AM-04               	Blood               	10 m	11.2204 g	11.4008 g
0.1804 g

AM-04               	Blood               	15 m	N.C.	N.C.	N.C.

AM-04               	Blood               	30 m	11.1966 g	11.3660 g
0.1694 g

AM-04               	Blood               	1 h	N.C.	N.C.	N.C.

AM-04               	Blood               	2 h	11.2190 g	11.4067 g	0.1877
g

AM-04               	Blood               	4 h	N.C.	N.C.	N.C.

AM-04               	Blood               	6 h	11.2026 g	11.4238 g	0.2212
g

AM-04               	Blood               	6.25 h	N.C.	N.C.	N.C.

AM-04               	Blood               	6.50 h	11.3147 g	11.5023 g
0.1876 g

AM-04               	Blood               	7 h	N.C.	N.C.	N.C.

AM-04               	Blood               	7.33 h	11.2080 g	11.3777 g
0.1697 g

AM-04               	Blood               	8 h	N.C.	N.C.	N.C.

AM-04               	Blood               	10 h	11.1735 g	11.3462 g
0.1727 g

AM-04               	Blood               	16 h	N.C.	N.C.	N.C.

AM-04               	Blood               	24 h	11.2187 g	11.3939 g
0.1752 g



Table 2 (contd).  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AM-05               	Blood               	Predose	11.3734 g	11.5553 g
0.1819 g

AM-05               	Blood               	5 m	N.C.	N.C.	N.C.

AM-05               	Blood               	10 m	11.1943 g	11.4195 g
0.2252 g

AM-05               	Blood               	15 m	N.C.	N.C.	N.C.

AM-05               	Blood               	30 m	11.1877 g	11.4057 g
0.2180 g

AM-05               	Blood               	1 h	N.C.	N.C.	N.C.

AM-05               	Blood               	2 h	11.3557 g	11.5411 g	0.1854
g

AM-05               	Blood               	4 h	N.C.	N.C.	N.C.

AM-05               	Blood               	6 h	11.1845 g	11.2590 g	0.0745
g

AM-05               	Blood               	6.25 h	N.C.	N.C.	N.C.

AM-05               	Blood               	6.50 h	11.2168 g	11.3994 g
0.1826 g

AM-05               	Blood               	7 h	N.C.	N.C.	N.C.

AM-05               	Blood               	7.33 h	11.3649 g	11.5585 g
0.1936 g

AM-05               	Blood               	8 h	N.C.	N.C.	N.C.

AM-05               	Blood               	10 h	11.2248 g	11.4093 g
0.1845 g

AM-05               	Blood               	16 h	N.C.	N.C.	N.C.

AM-05               	Blood               	24 h	11.4001 g	11.5802 g
0.1801 g

AM-06               	Blood               	Predose	11.3955 g	11.5799 g
0.1844 g

AM-06               	Blood               	5 m	N.C.	N.C.	N.C.

AM-06               	Blood               	10 m	11.3726 g	11.6361 g
0.2635 g

AM-06               	Blood               	10 m	11.3726 g	11.6361 g
0.2635 g

AM-06               	Blood               	15 m	N.C.	N.C.	N.C.

AM-06               	Blood               	30 m	11.3646 g	11.5919 g
0.2273 g

AM-06               	Blood               	1 h	N.C.	N.C.	N.C.

AM-06               	Blood               	2 h	11.1996 g	11.3722 g	0.1726
g

AM-06               	Blood               	4 h	N.C.	N.C.	N.C.

AM-06               	Blood               	6 h	11.3379 g	11.5769 g	0.2390
g

AM-06               	Blood               	6.25 h	N.C.	N.C.	N.C.

AM-06               	Blood               	6.50 h	11.1831 g	11.3885 g
0.2054 g

AM-06               	Blood               	7 h	N.C.	N.C.	N.C.

AM-06               	Blood               	7.33 h	11.2140 g	11.3992 g
0.1852 g

AM-06               	Blood               	8 h	N.C.	N.C.	N.C.

AM-06               	Blood               	10 h	11.1886 g	11.3758 g
0.1872 g

AM-06               	Blood               	16 h	N.C.	N.C.	N.C.

AM-06               	Blood               	24 h	11.2312 g	11.4147 g
0.1835 g



Table 2 (contd).  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AF-01               	Blood               	Predose	11.1291 g	11.3771 g
0.2480 g

AF-01               	Blood               	5 m	11.3310 g	11.5398 g	0.2088
g

AF-01               	Blood               	10 m	N.C.	N.C.	N.C.

AF-01               	Blood               	15 m	11.1447 g	11.3298 g
0.1851 g

AF-01               	Blood               	30 m	N.C.	N.C.	N.C.

AF-01               	Blood               	1 h	11.2324 g	11.4361 g	0.2037
g

AF-01               	Blood               	2 h	N.C.	N.C.	N.C.

AF-01               	Blood               	4 h	11.1913 g	11.3916 g	0.2003
g

AF-01               	Blood               	6 h	N.C.	N.C.	N.C.

AF-01               	Blood               	6.25 h	11.1559 g	11.3721 g
0.2162 g

AF-01               	Blood               	6.50 h	N.C.	N.C.	N.C.

AF-01               	Blood               	7 h	11.3248 g	11.5011 g	0.1763
g

AF-01               	Blood               	7.33 h	N.C.	N.C.	N.C.

AF-01               	Blood               	8 h	11.2111 g	11.3844 g	0.1733
g

AF-01               	Blood               	10 h	N.C.	N.C.	N.C.

AF-01               	Blood               	16 h	11.2184 g	11.4104 g
0.1920 g

AF-01               	Blood               	24 h	N.C.	N.C.	N.C.

AF-02               	Blood               	Predose	11.3486 g	11.5351 g
0.1865 g

AF-02               	Blood               	5 m	11.1955 g	11.4358 g	0.2403
g

AF-02               	Blood               	10 m	N.C.	N.C.	N.C.

AF-02               	Blood               	15 m	11.3651 g	11.5766 g
0.2115 g

AF-02               	Blood               	30 m	N.C.	N.C.	N.C.

AF-02               	Blood               	1 h	11.2009 g	11.4147 g	0.2138
g

AF-02               	Blood               	2 h	N.C.	N.C.	N.C.

AF-02               	Blood               	4 h	11.1653 g	11.3543 g	0.1890
g

AF-02               	Blood               	6 h	N.C.	N.C.	N.C.

AF-02               	Blood               	6.25 h	11.3460 g	11.5281 g
0.1821 g

AF-02               	Blood               	6.50 h	N.C.	N.C.	N.C.

AF-02               	Blood               	7 h	11.4304 g	11.6057 g	0.1753
g

AF-02               	Blood               	7.33 h	N.C.	N.C.	N.C.

AF-02               	Blood               	8 h	11.4004 g	11.5626 g	0.1622
g

AF-02               	Blood               	10 h	N.C.	N.C.	N.C.

AF-02               	Blood               	16 h	11.2027 g	11.3560 g
0.1533 g

AF-02               	Blood               	24 h	N.C.	N.C.	N.C.



Table 2 (contd).  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AF-03               	Blood               	Predose	11.2306 g	11.3887 g
0.1581 g

AF-03               	Blood               	5 m	11.1761 g	11.3002 g	0.1241
g

AF-03               	Blood               	10 m	N.C.	N.C.	N.C.

AF-03               	Blood               	15 m	11.2173 g	11.3713 g
0.1540 g

AF-03               	Blood               	30 m	N.C.	N.C.	N.C.

AF-03               	Blood               	1 h	11.1616 g	11.3718 g	0.2102
g

AF-03               	Blood               	2 h	N.C.	N.C.	N.C.

AF-03               	Blood               	4 h	11.2198 g	11.4459 g	0.2261
g

AF-03               	Blood               	6 h	N.C.	N.C.	N.C.

AF-03               	Blood               	6.25 h	11.2496 g	11.4027 g
0.1531 g

AF-03               	Blood               	6.50 h	N.C.	N.C.	N.C.

AF-03               	Blood               	7 h	11.2221 g	11.3962 g	0.1741
g

AF-03               	Blood               	7.33 h	N.C.	N.C.	N.C.

AF-03               	Blood               	8 h	11.2496 g	11.4627 g	0.2131
g

AF-03               	Blood               	10 h	N.C.	N.C.	N.C.

AF-03               	Blood               	16 h	11.2962 g	11.4679 g
0.1717 g

AF-03               	Blood               	24 h	N.C.	N.C.	N.C.

AF-04               	Blood               	Predose	11.2236 g	11.4068 g
0.1832 g

AF-04               	Blood               	5 m	N.C.	N.C.	N.C.

AF-04               	Blood               	10 m	11.3813 g	11.5701 g
0.1888 g

AF-04               	Blood               	15 m	N.C.	N.C.	N.C.

AF-04               	Blood               	30 m	11.1526 g	11.3641 g
0.2115 g

AF-04               	Blood               	1 h	N.C.	N.C.	N.C.

AF-04               	Blood               	2 h	11.1605 g	11.3137 g	0.1532
g

AF-04               	Blood               	4 h	N.C.	N.C.	N.C.

AF-04               	Blood               	6 h	11.2091 g	11.3934 g	0.1843
g

AF-04               	Blood               	6.25 h	N.C.	N.C.	N.C.

AF-04               	Blood               	6.50 h	11.3755 g	11.5460 g
0.1705 g

AF-04               	Blood               	7 h	N.C.	N.C.	N.C.

AF-04               	Blood               	7.33 h	11.3771 g	11.5487 g
0.1716 g

AF-04               	Blood               	8 h	N.C.	N.C.	N.C.

AF-04               	Blood               	10 h	11.2255 g	11.3967 g
0.1712 g

AF-04               	Blood               	16 h	N.C.	N.C.	N.C.

AF-04               	Blood               	24 h	11.2811 g	11.4613 g
0.1802 g



Table 2 (contd).  Blood Sample Weights from Group A.

Subject	Sample	Time	Pot wt	Sample  wt	Corrected

Sample Weight

AF-05               	Blood               	Predose	11.3193 g	11.4684 g
0.1491 g

AF-05               	Blood               	5 m	N.C.	N.C.	N.C.

AF-05               	Blood               	10 m	11.3289 g	11.5320 g
0.2031 g

AF-05               	Blood               	15 m	N.C.	N.C.	N.C.

AF-05               	Blood               	30 m	11.2137 g	11.3794 g
0.1657 g

AF-05               	Blood               	1 h	N.C.	N.C.	N.C.

AF-05               	Blood               	2 h	11.1775 g	11.3433 g	0.1658
g

AF-05               	Blood               	4 h	N.C.	N.C.	N.C.

AF-05               	Blood               	6 h	11.3272 g	11.5219 g	0.1947
g

AF-05               	Blood               	6.25 h	N.C.	N.C.	N.C.

AF-05               	Blood               	6.50 h	11.3682 g	11.5349 g
0.1667 g

AF-05               	Blood               	7 h	N.C.	N.C.	N.C.

AF-05               	Blood               	7.33 h	11.2059 g	11.3884 g
0.1825 g

AF-05               	Blood               	8 h	N.C.	N.C.	N.C.

AF-05               	Blood               	10 h	11.2451 g	11.4289 g
0.1838 g

AF-05               	Blood               	16 h	N.C.	N.C.	N.C.

AF-05               	Blood               	24 h	11.2257 g	11.4078 g
0.1821 g

AF-06               	Blood               	Predose	11.3616 g	11.5308 g
0.1692 g

AF-06               	Blood               	5 m	N.C.	N.C.	N.C.

AF-06               	Blood               	10 m	11.1749 g	11.3078 g
0.1329 g

AF-06               	Blood               	15 m	N.C.	N.C.	N.C.

AF-06               	Blood               	30 m	11.1923 g	11.4146 g
0.2223 g

AF-06               	Blood               	1 h	N.C.	N.C.	N.C.

AF-06               	Blood               	2 h	11.1812 g	11.3702 g	0.1890
g

AF-06               	Blood               	4 h	N.C.	N.C.	N.C.

AF-06               	Blood               	6 h	11.1287 g	11.3020 g	0.1733
g

AF-06               	Blood               	6.25 h	N.C.	N.C.	N.C.

AF-06               	Blood               	6.50 h	11.1532 g	11.3253 g
0.1721 g

AF-06               	Blood               	7 h	N.C.	N.C.	N.C.

AF-06               	Blood               	7.33 h	11.1741 g	11.4254 g
0.2513 g

AF-06               	Blood               	8 h	N.C.	N.C.	N.C.

AF-06               	Blood               	10 h	11.2900 g	11.4425 g
0.1525 g

AF-06               	Blood               	16 h	N.C.	N.C.	N.C.

AF-06               	Blood               	24 h	11.2421 g	11.4275 g
0.1854 g



Table 3.  Low Concentration Calibration Curve for DIPE in Blood. 



 	Peak Area







Sample I.D.	Standard/QC I.D 	 Conc. (ug/ml)	DIPE	MTBE	Peak Area Ratio
Cal. Conc. (ug/ml)	Mean	SD	RSD% (Precision)	Accuracy (%)

12322-127A	Blood blank	0	0	0	n/a	n/a	n/a	n/a	n/a	n/a

12322-128A	Blood blank	0	0	0	n/a	n/a	-	-	-	n/a

12322-133A	Blood blank	0	0	0	n/a	n/a	-	-	-	n/a

12322-127B	Blood ISTD blank	0	0	2214393	0	n/a	n/a	n/a	n/a	n/a

12322-128B	Blood ISTD blank	0	0	2158058	0	n/a	-	-	-	n/a

12322-133B	Blood ISTD blank	0	0	2035366	0	n/a	-	-	-	n/a

12322-127C	Std A1 	0.0898	11525	2122933	0.00543	0.0911	0.0908	0.00166
1.83%	101%

12322-128C	Std A1 	0.0898	11854	2153947	0.00550	0.0923	-	-	-	103%

12322-133C	Std A1 	0.0898	10282	1937595	0.00531	0.0890	-	-	-	99.1%

12322-127D	Std B1	0.224	29693	2145488	0.0138	0.231	0.227	0.00412	1.82%
103%

12322-128D	Std B1	0.224	27954	2078860	0.0134	0.225



100%

12322-133D	Std B1	0.224	26653	1991375	0.0134	0.224	 	 	 	100%

12322-127E 	Std A2	0.457	58885	2156926	0.0273	0.456	0.447	0.00909	2.03%
100%

12322-128E 	Std A2	0.457	55824	2083004	0.0268	0.448	-	-	-	98.0%

12322-133E	Std A2	0.457	52944	2019835	0.0262	0.438	-	-	-	95.8%

12322-127F	Std B2	0.910	112752	2083496	0.0541	0.904	0.895	0.00974	1.09%
99.3%

12322-128F	Std B2	0.910	113998	2120200	0.0538	0.898



98.7%

12322-133F	Std B2	0.910	105692	1995024	0.0530	0.88	 	 	 	97.2%

12322-127G	Std A3	2.33	302874	2038370	0.149	2.48	2.38	0.0926	3.90%	106%

12322-128G	Std A3	2.33	279697	1990241	0.141	2.35



101%

12322-133G	Std A3	2.33	275706	1998611	0.138	2.30	 	 	 	98.8%

12322-127H	Std B3	4.61	562576	2000450	0.281	4.69	4.58	0.100	2.19%	102%

12322-128H	Std B3	4.61	581850	2135947	0.272	4.55	-	-	-	98.6%

12322-133H	Std B3	4.61	535866	1986368	0.270	4.50	-	-	-	97.7%

12322-132-13	LQC	0.457	60533	2175613	0.0278	0.465	-	-	-	102%

12322-132-14	LQC	0.457	56369	2125207	0.0265	0.443	-	-	-	97.0%

12322-130-37	MQC	4.61	584614	2141927	0.273	4.56	-	-	-	98.8%

12322-130-38	MQC	4.61	579786	2146326	0.270	4.51	-	-	-	97.8%













	  a   INTERCEPT	-0.000027814









	b     SLOPE	0.059915









	r	0.9996







	

Table 4.  High Concentration Calibration Curve for DIPE in Blood.



	Peak Area







Sample I.D.	Standard/QC I.D 	 Conc. (ug/ml)	DIPE	MTBE	Peak Area Ratio
Cal. Conc. (ug/ml)	Mean	SD	RSD% (Precision)	Accuracy (%)

12322-127H	Std B3	4.61	562576	2000450	0.281	5.04	4.94	0.087	1.76%	109%

12322-128H	Std B3	4.61	581850	2135947	0.272	4.91	-	-	-	107%

12322-133H	Std B3	4.61	535866	1986368	0.270	4.87	-	-	-	106%

12322-127I	Std A4	9.49	1261083	2033960	0.620	9.94	9.71	0.234	2.41%	105%

12322-128I	Std A4	9.49	1252607	2073581	0.604	9.71	-	-	-	102%

12322-133I	Std A4	9.49	1143785	1946173	0.588	9.47	-	-	-	100%

12322-127J	Std B4	23.6	3203037	2025586	1.58	23.8	22.7	1.07	4.70%	101%

12322-128J	Std B4	23.6	3127453	2093341	1.49	22.6	-	-	-	95.7%

12322-133J	Std B4	23.6	2694565	1878234	1.43	21.7	-	-	-	92.0%

12322-127K	Std A5	48.4	6861748	2011540	3.41	50.3	47.0	2.86	6.09%	104%

12322-128K	Std A5	48.4	6413305	2075118	3.09	45.7	-	-	-	94.4%

12322-133K	Std A5	48.4	6075548	1992223	3.05	45.1	-	-	-	93.1%

12322-127L	Std B5	96.8	13281090	1989035	6.68	97.5	91.5	5.27	5.76%	101%

12322-128L	Std B5	96.8	12547672	2068516	6.07	88.7	-	-	-	91.6%

12322-133L	Std B5	96.8	11245967	1865371	6.03	88.2	-	-	-	91.1%

12322-127M	Std A6	247	35964910	1925776	18.7	271	254	17.61	6.93%	110%

12322-128M	Std A6	247	36519922	2072875	17.6	256	-	-	-	103%

12322-133M	Std A6	247	29531463	1817627	16.2	236	-	-	-	95.4%

12322-129-29	HQC	96.8	16459861	2911883	5.65	82.7	-	-	-	85.5%

12322-129-30	HQC	96.8	13359906	2473443	5.40	79.1	-	-	-	81.7%



























  a   INTERCEPT	-0.067191









	b     SLOPE	0.069144









	r	0.997







	



Table 5.  Calibration Curve for Isopropanol in Blood.

 	 	 	Peak Area	 	 	 	 	 	 

Sample I.D.	Standard/QC I.D 	 Conc. (ug/ml)	Isopropanol	1-Propanol	Peak
Area Ratio	Cal. Conc. (ug/ml)	Mean	SD	RSD% (Precision)	Accuracy (%)

12322-127H	Std B3	4.31	309729	2070660	0.150	5.21	5.17	0.038	0.73%	120%

12322-128H	Std B3	4.31	302155	2061227	0.147	5.15	-	-	-	-

12322-133H	Std B3	4.31	293968	2007689	0.146	5.15	-	-	-	-

12322-127I	Std A4	9.00	709288	2141030	0.331	9.08	8.98	0.091	1.01%	99.7%

12322-128I	Std A4	9.00	685643	2121227	0.323	8.91	-	-	-	-

12322-133I	Std A4	9.00	632539	1947290	0.325	8.94	-	-	-	-

12322-127J	Std B4	22.1	1808774	2147270	0.842	19.9	20.1	0.151	0.750%
91.1%

12322-128J	Std B4	22.1	1794299	2098258	0.855	20.2	-	-	-	-

12322-133J	Std B4	22.1	1617027	1893249	0.854	20.2	-	-	-	-

12322-127K	Std A5	45.9	4032278	2088233	1.93	43.1	41.6	1.35	3.23%	90.7%

12322-128K	Std A5	45.9	3673564	2032197	1.81	40.5	-	-	-	-

12322-133K	Std A5	45.9	3776924	2047611	1.84	41.3	-	-	-	-

12322-127L	Std B5	90.5	8162809	2120148	3.85	83.9	85.1	1.19	1.40%	94.0%

12322-128L	Std B5	90.5	8307486	2096739	3.96	86.3	-	-	-	-

12322-133L	Std B5	90.5	8181688	2095536	3.90	85	-	-	-	-

12322-126M	Std A6	235	23370217	2076797	11.3	241	245	4.70	1.91%	105%

12322-127M	Std A6	235	22695441	1941824	11.7	251	-	-	-	-

12322-128M	Std A6	235	21694423	1902916	11.4	245	-	-	-	-

12322-130-37	MQC	4.31	314193	2086971	0.151	5.23	-	-	-	121%

12322-130-38	MQC	4.31	333890	2221608	0.150	5.23	-	-	-	121%

12322-129-29	HQC	90.5	9881942	2686808	3.68	80.3	-	-	-	88.7%

12322-129-30	HQC	90.5	8868719	2445017	3.63	79.2	-	-	-	87.5%



























  a   INTERCEPT	-0.095588









	b     SLOPE	0.047019









	r	0.997







	

Table 6.  Calibration Curve for Acetone in Blood.

 	 	 	Peak Area	 	 	 	 	 	 

Sample I.D.	Standard/QC I.D 	 Conc. (ug/ml)	Acetone	1-Propanol	Peak Area
Ratio	Cal. Conc. (ug/ml)	Mean	SD	RSD% (Precision)	Accuracy (%)

12322-127G	Std A3	2.21	126646	2033231	0.0623	2.51	2.48	0.0319	1.29%	112%

12322-128G	Std A3	2.21	118493	1949997	0.0608	2.45	-	-	-	-

12322-133G	Std A3	2.21	125349	2049143	0.0612	2.47	-	-	-	-

12322-127H	Std B3	4.30	223600	2070660	0.108	4.36	4.40	0.0353	0.803%	102%

12322-128H	Std B3	4.30	224879	2061227	0.109	4.41	-	-	-	-

12322-133H	Std B3	4.30	220256	2007689	0.110	4.43	-	-	-	-

12322-127I	Std A4	9.02	454345	2141030	0.212	8.57	8.70	0.190	2.19%	96.4%

12322-128I	Std A4	9.02	451733	2121227	0.213	8.60	-	-	-	-

12322-133I	Std A4	9.02	429772	1947290	0.221	8.92	-	-	-	-

12322-127J	Std B4	22.0	1085864	2147270	0.506	20.4	20.9	0.397	1.90%	95.0%

12322-128J	Std B4	22.0	1095322	2098258	0.522	21.1	-	-	-	-

12322-133J	Std B4	22.0	990823	1893249	0.523	21.2	-	-	-	-

12322-127K	Std A5	46.0	2305559	2088233	1.10	44.6	44.0	0.524	1.19%	95.7%

12322-128K	Std A5	46.0	2203661	2032197	1.08	43.8	-	-	-	-

12322-133K	Std A5	46.0	2210602	2047611	1.08	43.6	-	-	-	-

12322-127L	Std B5	90.3	4532539	2120148	2.14	86.4	86.2	2.41	2.80%	95.5%

12322-128L	Std B5	90.3	4591627	2096739	2.19	88.5	-	-	-	-

12322-133L	Std B5	90.3	4339333	2095536	2.07	84	-	-	-	-

12322-126M	Std A6	235	12300203	2076797	5.92	239	242	8.74	3.61%	103%

12322-127M	Std A6	235	12105819	1941824	6.23	252	-	-	-	-

12322-128M	Std A6	235	11073151	1902916	5.82	235	-	-	-	-

12322-130-37	MQC	4.30	221846	2086971	0.106	4.29	-	-	-	100%

12322-130-38	MQC	4.30	241029	2221608	0.108	4.38	-	-	-	102%

12322-129-29	HQC	90.3	5361227	2686808	2.00	80.7	-	-	-	89.3%

12322-129-30	HQC	90.3	4744139	2445017	1.94	78	-	-	-	86.9%



























  a   INTERCEPT	0.00013973









	b     SLOPE	0.024733









	r	0.999







	

Table 7.  DIPE Blood Concentration Analysis for Groups A.

Rat.	Time

point	DIPE 

Peak Area	MTBE

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 01	Predose	0	3305500	0	below LOQ	0.1715	n/a

	5 min	3942626	3094095	1.27	19.4	0.1451	13.4

	15 min	10284961	2726284	3.77	55.5	0.1815	30.6

	1 hr	11169127	2352305	4.75	69.6	0.1883	37.0

	4hr	16109055	2154766	7.48	109	0.1980	55.1

	6.25 hr	6178612	2255680	2.74	40.6	0.1646	24.7

	7 hr	1823281	2073026	0.880	14.7	0.1698	8.65

	8 hr	366955	2163484	0.170	2.83	0.1497	1.89

 	16 hr	3908	1792938	0.00218	below LOQ	0.1602	n/a

AM 02	Predose	0	3220242	0	below LOQ	0.1612	n/a

	5 min	9760022	3004415	3.25	48.0	0.2109	22.7

	15 min	13281846	2657842	5.00	73.2	0.2103	34.8

	1 hr	23604618	2422594	9.74	142	0.3015	47.1

	4hr	13284866	2198086	6.04	88.4	0.1649	53.6

	6.25 hr	3309760	2183125	1.52	22.9	0.1585	14.4

	7 hr	1751996	2074241	0.845	13.2	0.1769	7.45

	8 hr	399385	1912997	0.209	3.48	0.1489	2.34

 	16 hr	18213	1895367	0.00961	below LOQ	0.1800	n/a

AM 03	Predose	0	3125677	0	below LOQ	0.1952	n/a

	5 min	7370270	2937781	2.51	37.3	0.1710	21.8

	15 min	11490102	2682406	4.28	62.9	0.2109	29.8

	1 hr	16872653	2289260	7.37	108	0.2168	49.6

	4hr	17905650	2155261	8.31	121	0.2073	58.4

	6.25 hr	3369772	2182099	1.54	23.3	0.1584	14.7

	7 hr	1731385	2044830	0.847	13.2	0.1740	7.60

	8 hr	534386	2071092	0.258	4.31	0.1798	2.40

 	16 hr	4515	1884535	0.00240	below LOQ	0.1570	n/a

Table 7 (continued).  ETBE DIPE Blood Concentration Analysis for Group
A.

Rat.	Time

point	DIPE 

Peak Area	MTBE

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 04	Predose	0	3141737	0	below LOQ	0.1625	n/a

	10 min	6634863	2864181	2.32	34.5	0.1804	19.1

	30 min	7478194	2501719	2.99	44.2	0.1694	26.1

	2 hr	11532703	2276394	5.07	74.2	0.1877	39.6

	6 hr	16647985	2106319	7.90	115	0.2212	52.1

	6.5 hr	3001728	2155520	1.39	21.1	0.1876	11.3

	7.33 hr	1252155	2220162	0.564	9.13	0.1697	5.38

	10 hr	177616	2061463	0.0862	1.44	0.1727	0.833

 	24 hr	0	2006661	0.000	below LOQ	0.1752	n/a

AM 05	Predose	0	3076076	0	below LOQ	0.1819	n/a

	10 min	11508463	2772270	4.15	61.0	0.2252	27.1

	30 min	16985066	2468288	6.88	100	0.2180	46.1

	2 hr	15454012	2326258	6.64	97.1	0.1854	52.3

	6 hr	2817350	2046662	1.38	20.9	0.0745	28.0

	6.5 hr	2061183	2113931	0.975	15.1	0.1826	8.25

	7.33 hr	729460	2040999	0.357	6.14	0.1936	3.17

	10 hr	72643	2018958	0.0360	0.601	0.1845	0.326

 	24 hr	0	1776471	0.000	below LOQ	0.1801	n/a

AM 06	Predose	0	3063913	0	below LOQ	0.1844	n/a

	10 min	14799587	2794446	5.30	77.6	0.2635	29.4

	30 min	16164176	2494808	6.48	94.7	0.2273	41.7

	2 hr	14031744	2189712	6.41	93.6	0.1726	54.3

	6 hr	21078163	2053273	10.3	149	0.2390	62.5

	6.5 hr	3341880	2133667	1.57	23.6	0.2054	11.5

	7.33 hr	653874	2087767	0.313	5.50	0.1852	2.97

	10 hr	76651	1949776	0.0393	0.66	0.1872	0.351

 	24 hr	0	1782700	0.000	below LOQ	0.1835	n/a

Table 7 (continued).  ETBE DIPE Blood Concentration Analysis for Group
A.

Rat.	Time

point	DIPE 

Peak Area	MTBE

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 01	Predose	0	3043812	0	below LOQ	0.2480	n/a

	5 min	8818210	2820179	3.13	46.2	0.2088	22.1

	15 min	10416878	2583392	4.03	59.3	0.1851	32.0

	1 hr	14503744	2408498	6.02	88.1	0.2037	43.2

	4hr	16260076	2161490	7.52	110	0.2003	54.8

	6.25 hr	5613786	2137156	2.63	39.0	0.2162	18.0

	7 hr	1173091	2071197	0.566	9.16	0.1763	5.20

	8 hr	404239	1975565	0.205	3.42	0.1733	1.97

 	16 hr	22623	1806051	0.0125	below LOQ	0.1920	n/a

AF 02	Predose	0	3083673	0	below LOQ	0.1865	n/a

	5 min	7871770	2863675	2.75	40.7	0.2403	16.9

	15 min	10413512	2643903	3.94	57.9	0.2115	27.4

	1 hr	18600188	2434213	7.64	111	0.2138	52.1

	4hr	16437024	2112136	7.78	114	0.1890	60.1

	6.25 hr	5113255	2084851	2.45	36.4	0.1821	20.0

	7 hr	1435584	2046806	0.70	11.1	0.1753	6.34

	8 hr	259829	1862016	0.140	2.33	0.1622	1.44

 	16 hr	0	1806061	0.000	below LOQ	0.1533	n/a

AF 03	Predose	0	2976122	0	below LOQ	0.1581	n/a

	5 min	5179417	2901591	1.79	26.8	0.1241	21.6

	15 min	9835262	2659346	3.70	54.5	0.1540	35.4

	1 hr	15868117	2323506	6.83	99.7	0.2102	47.5

	4hr	22848033	2201343	10.4	151	0.2261	66.8

	6.25 hr	3962996	2158089	1.84	27.5	0.1531	18.0

	7 hr	1564184	2064230	0.758	11.9	0.1741	6.85

	8 hr	608280	2167471	0.281	5.03	0.2131	2.36

 	16 hr	3888	1810056	0.00215	below LOQ	0.1717	n/a

 Table 7 (continued).  ETBE DIPE Blood Concentration Analysis for Group
A.

Rat.	Time

point	DIPE 

Peak Area	MTBE

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 04	Predose	0	3026192	0	below LOQ	0.1832	n/a

	10 min	8856549	2773431	3.19	47.2	0.1888	25.0

	30 min	15766622	2586291	6.10	89.1	0.2115	42.1

	2 hr	13960100	2236237	6.24	91.3	0.1532	59.6

	6 hr	16325203	2031561	8.04	117	0.1843	63.6

	6.5 hr	2310642	2112871	1.09	16.8	0.1705	9.85

	7.33 hr	757162	2029278	0.373	6.37	0.1716	3.71

	10 hr	82489	2028032	0.0407	0.679	0.1712	0.397

 	24 hr	0	1515234	0.000	below LOQ	0.1802	n/a

AF 05	Predose	0	3050805	0	below LOQ	0.1491	n/a

	10 min	11816192	2789584	4.24	62.2	0.2031	30.6

	30 min	12151980	2539713	4.78	70.2	0.1657	42.3

	2 hr	16836252	2307750	7.30	106	0.1658	64.2

	6 hr	19612248	2042061	9.60	140	0.1947	71.8

	6.5 hr	2553966	2042423	1.25	19.1	0.1667	11.4

	7.33 hr	1033665	1961449	0.527	8.59	0.1825	4.71

	10 hr	90528	2023204	0.0447	0.747	0.1838	0.407

 	24 hr	0	1451432	0.000	below LOQ	0.1821	n/a

AF 06	Predose	0	3018009	0	below LOQ	0.1692	n/a

	10 min	8351910	2776813	3.01	44.5	0.1329	33.5

	30 min	15718575	2481371	6.33	92.6	0.2223	41.6

	2 hr	16424573	2215625	7.41	108	0.1890	57.2

	6 hr	15057861	2065393	7.29	106	0.1733	61.4

	6.5 hr	3573258	2095249	1.71	25.6	0.1721	14.9

	7.33 hr	1543333	2009887	0.768	12.1	0.2513	4.81

	10 hr	65336	2000918	0.0327	0.545	0.1525	0.358

 	24 hr	0	1394642	0.000	below LOQ	0.1854	n/a

Table 8.  Isopropanol Blood Concentration Analysis for Group A.

Rat.	Time

point	Isopropanol 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 01	Predose	6272	2153513	0.00291	below LOQ	0.1715	n/a

	5 min	109777	2380795	0.0461	below LOQ	0.1451	n/a

	15 min	351929	1766360	0.199	6.27	0.1815	3.45

	1 hr	1445382	1573428	0.919	21.6	0.1883	11.5

	4hr	5681189	1352656	4.20	91.4	0.1980	46.1

	6.25 hr	8561604	1647935	5.20	113	0.1646	68.4

	7 hr	6432824	1461713	4.40	95.6	0.1698	56.3

	8 hr	3721832	1621117	2.30	50.9	0.1497	34.0

 	16 hr	115326	1437329	0.0802	below LOQ	0.1602	n/a

AM 02	Predose	4018	2146112	0.00187	below LOQ	0.1612	n/a

	5 min	151958	1654781	0.0918	below LOQ	0.2109	n/a

	15 min	310509	1543333	0.201	6.31	0.2103	3.00

	1 hr	1526965	1028884	1.48	33.6	0.3015	11.1

	4hr	4547418	1579939	2.88	63.2	0.1649	38.4

	6.25 hr	7007494	1712280	4.09	89.1	0.1585	56.2

	7 hr	5108536	1450585	3.52	76.9	0.1769	43.5

	8 hr	2980650	1617537	1.84	41.2	0.1489	27.7

 	16 hr	90571	1301098	0.0696	below LOQ	0.1800	n/a

AM 03	Predose	5380	1854237	0.00290	below LOQ	0.1952	n/a

	5 min	175658	1978677	0.0888	below LOQ	0.1710	n/a

	15 min	385625	1495362	0.258	7.52	0.2109	3.56

	1 hr	1541485	1319785	1.17	26.9	0.2168	12.4

	4hr	5138002	1272284	4.04	87.9	0.2073	42.4

	6.25 hr	8226552	1717442	4.79	104	0.1584	65.6

	7 hr	6370190	1501241	4.24	92.3	0.1740	53.0

	8 hr	4429311	1594458	2.78	61.1	0.1798	34.0

 	16 hr	77984	1468074	0.0531	below LOQ	0.1570	n/a

Table 8 (continued).  Isopropanol Blood Concentration Analysis for Group
A.

Rat.	Time

point	Isopropanol 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 04	Predose	6838	2106071	0.00325	below LOQ	0.1625	n/a

	10 min	215829	1980354	0.109	below LOQ	0.1804	n/a

	30 min	488328	1750458	0.279	7.97	0.1694	4.70

	2 hr	2157660	1492442	1.45	32.8	0.1877	17.5

	6 hr	7972351	1210042	6.59	142	0.2212	64.3

	6.5 hr	6772101	1428055	4.74	103	0.1876	54.8

	7.33 hr	4637067	1579500	2.94	64.5	0.1697	38.0

	10 hr	940207	1529728	0.615	15.1	0.1727	8.75

 	24 hr	3843	1413218	0.00272	below LOQ	0.1752	n/a

AM 05	Predose	3518	1933430	0.00182	below LOQ	0.1819	n/a

	10 min	244913	1511261	0.162	5.48	0.2252	2.43

	30 min	795402	1478297	0.538	13.5	0.2180	6.18

	2 hr	3048080	1479577	2.06	45.8	0.1854	24.7

	6 hr	5527552	2805396	1.97	43.9	0.0745	59.0

	6.5 hr	8254324	1433356	5.76	125	0.1826	68.2

	7.33 hr	5463418	1321156	4.14	90.0	0.1936	46.5

	10 hr	954680	1449282	0.659	16.0	0.1845	8.70

 	24 hr	3161	1314654	0.00240	below LOQ	0.1801	n/a

AM 06	Predose	5676	1923945	0.00295	below LOQ	0.1844	n/a

	10 min	344130	1319405	0.261	7.58	0.2635	2.88

	30 min	836825	1338377	0.625	15.3	0.2273	6.74

	2 hr	2956336	1535211	1.93	43.0	0.1726	24.9

	6 hr	9668514	1155596	8.37	180	0.2390	75.3

	6.5 hr	8433691	1319920	6.39	138	0.2054	67.1

	7.33 hr	5640666	1401146	4.03	87.7	0.1852	47.3

	10 hr	1089471	1404476	0.776	18.5	0.1872	9.90

 	24 hr	3276	1290696	0.00254	below LOQ	0.1835	n/a

Table 8 (continued).  Isopropanol Blood Concentration Analysis for Group
A.

Rat.	Time

point	Isopropanol 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 01	Predose	4258	1870330	0.00228	below LOQ	0.2480	n/a

	5 min	80094	1646387	0.0486	below LOQ	0.2088	n/a

	15 min	175601	1669197	0.105	below LOQ	0.1851	n/a

	1 hr	537971	1418766	0.379	10.1	0.2037	4.96

	4hr	2139912	1323597	1.62	36.4	0.2003	18.2

	6.25 hr	4187519	1254062	3.34	73.1	0.2162	33.8

	7 hr	2459573	1447194	1.70	38.2	0.1763	21.7

	8 hr	1019824	1430873	0.713	17.2	0.1733	9.92

 	16 hr	7248	1258028	0.00576	below LOQ	0.1920	n/a

AF 02	Predose	4955	1867624	0.00265	below LOQ	0.1865	n/a

	5 min	87060	1462557	0.0595	below LOQ	0.2403	n/a

	15 min	164656	1488895	0.111	below LOQ	0.2115	n/a

	1 hr	508099	1405743	0.361	9.72	0.2138	4.55

	4hr	2124810	1340890	1.58	35.7	0.1890	18.9

	6.25 hr	3773344	1421113	2.66	58.5	0.1821	32.1

	7 hr	2740403	1442899	1.90	42.4	0.1753	24.2

	8 hr	1104185	1535827	0.719	17.3	0.1622	10.7

 	16 hr	0	1518048	0.000	below LOQ	0.1533	n/a

AF 03	Predose	4303	2114181	0.00204	below LOQ	0.1581	n/a

	5 min	60845	2478779	0.0245	below LOQ	0.1241	n/a

	15 min	178917	1929727	0.0927	below LOQ	0.1540	n/a

	1 hr	657330	1339129	0.491	12.5	0.2102	5.93

	4hr	3357579	1194444	2.81	61.8	0.2261	27.3

	6.25 hr	4856392	1691576	2.87	63.1	0.1531	41.2

	7 hr	3566768	1498467	2.38	52.7	0.1741	30.2

	8 hr	1732491	1245271	1.39	31.6	0.2131	14.8

 	16 hr	4547	1376268	0.00330	below LOQ	0.1717	n/a

 Table 8 (continued).  Isopropanol Blood Concentration Analysis for
Group A.

Rat.	Time

point	Isopropanol 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 04	Predose	3375	1876350	0.00180	below LOQ	0.1832	n/a

	10 min	125400	1738855	0.0721	below LOQ	0.1888	n/a

	30 min	342561	1460313	0.235	7.02	0.2115	3.32

	2 hr	1216382	1711152	0.711	17.2	0.1532	11.2

	6 hr	3624672	1348619	2.69	59.2	0.1843	32.1

	6.5 hr	2949339	1514401	1.95	43.5	0.1705	25.5

	7.33 hr	1503455	1442100	1.04	24.2	0.1716	14.1

	10 hr	192882	1468611	0.131	below LOQ	0.1712	n/a

 	24 hr	0	1176006	0.000	below LOQ	0.1802	n/a

AF 05	Predose	5016	2179453	0.00230	below LOQ	0.1491	n/a

	10 min	124944	1623682	0.0770	below LOQ	0.2031	n/a

	30 min	264987	1780808	0.149	5.20	0.1657	3.14

	2 hr	1128969	1597459	0.707	17.1	0.1658	10.3

	6 hr	3437636	1295821	2.65	58.5	0.1947	30.0

	6.5 hr	2758250	1565204	1.76	39.5	0.1667	23.7

	7.33 hr	1522278	1340694	1.14	26.2	0.1825	14.3

	10 hr	261068	1319854	0.198	6.24	0.1838	3.39

 	24 hr	0	1163884	0.000	below LOQ	0.1821	n/a

AF 06	Predose	5826	2016276	0.00289	below LOQ	0.1692	n/a

	10 min	137916	2246791	0.0614	below LOQ	0.1329	n/a

	30 min	379115	1386373	0.273	7.85	0.2223	3.53

	2 hr	1220027	1416451	0.861	20.4	0.1890	10.8

	6 hr	3606894	1404703	2.57	56.6	0.1733	32.7

	6.5 hr	3314092	1551243	2.14	47.5	0.1721	27.6

	7.33 hr	2032056	1060293	1.92	42.8	0.2513	17.0

	10 hr	281055	1761284	0.160	5.43	0.1525	3.56

 	24 hr	0	1062345	0.000	below LOQ	0.1854	n/a



Table 9.  Acetone Blood Concentration Analysis for Group A.

Rat.	Time

point	Acetone

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 01	Predose	270086	2153513	0.125	below LOQ	0.1715	n/a

	5 min	375279	2380795	0.158	6.37	0.1451	4.39

	15 min	1029684	1766360	0.583	23.6	0.1815	13.0

	1 hr	3296086	1573428	2.09	84.7	0.1883	45.0

	4hr	14568860	1352656	10.8	435	0.1980	220

	6.25 hr	21514425	1647935	13.1	528	0.1646	321

	7 hr	20743258	1461713	14.2	574	0.1698	338

	8 hr	19230404	1621117	11.9	480	0.1497	320

 	16 hr	4501539	1437329	3.13	127	0.1602	79.0

AM 02	Predose	180456	2146112	0.0841	3.39	0.1612	2.11

	5 min	549846	1654781	0.332	13.4	0.2109	6.37

	15 min	798701	1543333	0.518	20.9	0.2103	9.95

	1 hr	3979523	1028884	3.87	156	0.3015	51.9

	4hr	12062123	1579939	7.63	309	0.1649	187

	6.25 hr	19050666	1712280	11.1	450	0.1585	284

	7 hr	19021029	1450585	13.1	530	0.1769	300

	8 hr	17189719	1617537	10.6	430	0.1489	289

 	16 hr	3481263	1301098	2.68	108	0.1800	60.1

AM 03	Predose	184997	1854237	0.0998	4.03	0.1952	2.06

	5 min	455526	1978677	0.230	9.30	0.1710	5.44

	15 min	1147140	1495362	0.767	31.0	0.2109	14.7

	1 hr	3857093	1319785	2.92	118	0.2168	54.5

	4hr	13229788	1272284	10.4	420	0.2073	203

	6.25 hr	19661195	1717442	11.4	463	0.1584	292

	7 hr	19369795	1501241	12.9	522	0.1740	300

	8 hr	21034680	1594458	13.2	533	0.1798	297

 	16 hr	3466818	1468074	2.36	95.5	0.1570	60.8

Table 9 (continued).  Acetone Blood Concentration Analysis for Group A.

Rat.	Time

point	Acetone 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AM 04	Predose	151802	2106071	0.0721	2.91	0.1625	1.79

	10 min	681027	1980354	0.344	13.9	0.1804	7.70

	30 min	1652770	1750458	0.944	38.2	0.1694	22.5

	2 hr	6621080	1492442	4.44	179	0.1877	95.6

	6 hr	22100456	1210042	18.3	738	0.2212	334

	6.5 hr	20006287	1428055	14.0	566	0.1876	302

	7.33 hr	19441867	1579500	12.3	498	0.1697	293

	10 hr	14971899	1529728	9.79	396	0.1727	229

 	24 hr	117779	1413218	0.0833	3.36	0.1752	1.92

AM 05	Predose	143411	1933430	0.0742	2.99	0.1819	1.65

	10 min	661144	1511261	0.437	17.7	0.2252	7.85

	30 min	1950469	1478297	1.32	53.3	0.2180	24.5

	2 hr	7122622	1479577	4.81	195	0.1854	105

	6 hr	10322687	2805396	3.68	149	0.0745	200

	6.5 hr	21299372	1433356	14.9	601	0.1826	329

	7.33 hr	20830982	1321156	15.8	637	0.1936	329

	10 hr	15006981	1449282	10.4	419	0.1845	227

 	24 hr	88945	1314654	0.0677	2.73	0.1801	1.52

AM 06	Predose	181028	1923945	0.0941	3.80	0.1844	2.06

	10 min	898106	1319405	0.681	27.5	0.2635	10.4

	30 min	2197824	1338377	1.64	66.4	0.2273	29.2

	2 hr	6285399	1535211	4.09	166	0.1726	95.9

	6 hr	22661455	1155596	19.6	793	0.2390	332

	6.5 hr	21938553	1319920	16.6	672	0.2054	327

	7.33 hr	20723658	1401146	14.8	598	0.1852	323

	10 hr	15227985	1404476	10.8	438	0.1872	234

 	24 hr	88171	1290696	0.0683	2.76	0.1835	1.50

Table 9 (continued).  Acetone Blood Concentration Analysis for Group A.

Rat.	Time

point	Acetone 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 01	Predose	131976151802	18703302106071	0.07060.0721	2.852.91
0.24800.1625	1.151.79

	5 min	327787681027	16463871980354	0.1990.344	8.0413.9	0.20880.1804
3.857.70

	15 min	6175011652770	16691971750458	0.3700.944	15.038.2	0.18510.1694
8.0822.5

	1 hr	24895126621080	14187661492442	1.754.44	70.9179	0.20370.1877
34.895.6

	4hr	892614722100456	13235971210042	6.7418.3	273738	0.20030.2212	136334

	6.25 hr	1427354020006287	12540621428055	11.414.0	460566	0.21620.1876
213302

	7 hr	1210479719441867	14471941579500	8.3612.3	338498	0.17630.1697
192293

	8 hr	1124312214971899	14308731529728	7.869.79	318396	0.17330.1727
183229

 	16 hr	111294117779	12580281413218	0.08850.0833	3.573.36	0.19200.1752
1.861.92

AF 02	Predose	164632143411	18676241933430	0.08820.0742	3.562.99
0.18650.1819	1.911.65

	5 min	567774661144	14625571511261	0.3880.437	15.717.7	0.24030.2252
6.537.85

	15 min	8213441950469	14888951478297	0.5521.32	22.353.3	0.21150.2180
10.524.5

	1 hr	25992177122622	14057431479577	1.854.81	74.8195	0.21380.1854
35.0105

	4hr	814623710322687	13408902805396	6.083.68	246149	0.18900.0745	130200

	6.25 hr	1294981021299372	14211131433356	9.1114.9	368601	0.18210.1826
202329

	7 hr	1285611820830982	14428991321156	8.9115.8	360637	0.17530.1936
205329

	8 hr	1048503815006981	15358271449282	6.8310.4	276419	0.16220.1845
170227

 	16 hr	11186188945	15180481314654	0.07370.0677	2.972.73	0.15330.1801
1.941.52

AF 03	Predose	147114181028	21141811923945	0.06960.0941	2.813.80
0.15810.1844	1.782.06

	5 min	194811898106	24787791319405	0.07860.681	3.1727.5	0.12410.2635
2.5610.4

	15 min	5114922197824	19297271338377	0.2651.64	10.766.4	0.15400.2273
6.9629.2

	1 hr	26699396285399	13391291535211	1.994.09	80.6166	0.21020.1726
38.395.9

	4hr	1179167522661455	11944441155596	9.8719.6	399793	0.22610.2390	177332

	6.25 hr	1401576421938553	16915761319920	8.2916.6	335672	0.15310.2054
219327

	7 hr	1471044820723658	14984671401146	9.8214.8	397598	0.17410.1852
228323

	8 hr	1612954515227985	12452711404476	13.010.8	524438	0.21310.1872
246234

 	16 hr	7957888171	13762681290696	0.05780.0683	below LOQ2.76
0.17170.1835	n/a1.50

 Table 9  (continued). Acetone Blood Concentration Analysis for Group
A.

Rat.	Time

point	Acetone 

Peak Area	1-Propanol

Peak Area	Peak Area

Ratio	Cal. Conc.

((g/ml)	Sample

weight (g)	Corrected

Conc.

((g/ml)

AF 04	Predose	144203	1876350	0.0769	3.10	0.1832	1.69

	10 min	354288	1738855	0.204	8.23	0.1888	4.36

	30 min	1293392	1460313	0.886	35.8	0.2115	16.9

	2 hr	4690259	1711152	2.74	111	0.1532	72.3

	6 hr	13313353	1348619	9.87	399	0.1843	217

	6.5 hr	12520755	1514401	8.27	334	0.1705	196

	7.33 hr	11564909	1442100	8.02	324	0.1716	189

	10 hr	6852970	1468611	4.67	189	0.1712	110

 	24 hr	60026	1176006	0.0510	below LOQ	0.1802	n/a

AF 05	Predose	116074	2179453	0.0533	below LOQ	0.1491	n/a

	10 min	396178	1623682	0.244	9.86	0.2031	4.85

	30 min	889165	1780808	0.499	20.2	0.1657	12.2

	2 hr	4274073	1597459	2.68	108	0.1658	65.2

	6 hr	12281058	1295821	9.48	383	0.1947	197

	6.5 hr	10953458	1565204	7.00	283	0.1667	170

	7.33 hr	10930515	1340694	8.15	330	0.1825	181

	10 hr	7119040	1319854	5.39	218	0.1838	119

 	24 hr	68095	1163884	0.0585	below LOQ	0.1821	n/a

AF 06	Predose	167418	2016276	0.0830	3.35	0.1692	1.98

	10 min	429890	2246791	0.191	7.73	0.1329	5.82

	30 min	1618253	1386373	1.17	47.2	0.2223	21.2

	2 hr	4960176	1416451	3.50	142	0.1890	74.9

	6 hr	12933193	1404703	9.21	372	0.1733	215

	6.5 hr	13552770	1551243	8.74	353	0.1721	205

	7.33 hr	14730115	1060293	13.9	562	0.2513	224

	10 hr	7809518	1761284	4.43	179	0.1525	118

 	24 hr	132375	1062345	0.125	5.03	0.1854	2.71



Appendix J

Noncompartmental Pharmacokinetic Analysis

Note that this section will be updated with final version 

Calculated values from WinNonlin version 1.5 and their units

Rsq                                                   

Rsq_adjusted                                          

Corr_XY                                               

No_points_lambda_z                                 

Lambda_z                               1/hr         

Lambda_z_lower                           hr          

Lambda_z_upper                           hr          

HL_Lambda_z                              hr           

Tlag                                     hr          

Tmax                                     hr         

Cmax                                  ug/mL           

Cmax_D                          kg*ug/mL/mg           

Tlast                                    hr            

Clast                                 ug/mL          

AUClast                            hr*ug/mL           

AUCall                             hr*ug/mL             

AUCINF_obs                         hr*ug/mL         

AUCINF_D_obs                 hr*kg*ug/mL/mg              

AUC_%Extrap_obs                           %            

Vz_F_obs                              mL/kg        

Cl_F_obs                           mL/hr/kg        

AUCINF_pred                        hr*ug/mL           

AUCINF_D_pred                hr*kg*ug/mL/mg           

AUC_%Extrap_pred                          %           

Vz_F_pred                             L/kg          

Cl_F_pred                          L/hr/kg          

AUMClast                        hr*hr*ug/mL           

AUMCINF_obs                     hr*hr*ug/mL         

AUMC_%Extrap_obs                          %           

AUMCINF_pred                    hr*hr*ug/mL         

AUMC_%Extrap_pred                         %           

MRTlast                                  hr              

MRTINF_obs                               hr            

MRTINF_pred                              hr             

Kinetics of DIPE in Male and Female Rats exposed to 3600 ppm DIPE by
inhalation.

Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Female

Start Time: 20:22:01 07-26-2013

End Time:   20:22:02 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

TITLE 1

DIPE inhalation 3600 ppm

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 5

DTIME 0

NCONSTANTS 1

CONSTANTS 300

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 14

DATA 'WINNLIN.DAT'

BEGIN

DIPE inhalation 3600 ppm

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .8330E-01     20.22                            .8421      .7015E-01

  .1670         29.69                            2.931      .3482

  .2500         31.60                            5.474      .8818

  .5000         42.05                            14.68      4.497

  1.000         47.61                            37.09      21.66

  2.000         60.34                            91.07      105.8

  4.000         60.56                            212.0      468.7

  6.000         65.61                            338.1      1105.

  6.250         18.67                            348.7      1168.

  6.500         12.06                            352.5      1193.

  7.000     *   6.130      5.693      .4370      357.1      1223.     
1.000

  7.330     *   4.409      4.211      .1971      358.8      1236.     
1.000

  8.000     *   1.923      2.283     -.3608      360.9      1252.     
1.000

  10.00     *   .3870      .3673      .1972E-01  363.2      1271.     
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .9913

 Rsq(adjusted)                      .9869

 Corr(x:y)                         -.9956

 Tlag                               .0000

 Tmax                              6.0000

 Cmax                             65.6099

 No._points_Lambda_z                4

 Tlast                            10.0000

 Clast                              .3870

 AUClast                         363.2418

 Lambda_z                           .9136

 Lambda_z_lower                    7.0000

 Lambda_z_upper                   10.0000

 t1/2_Lambda_z                      .7587

 AUCall                          363.2418

 AUCINF(observed)                363.6654

 AUCINF(observed)/D                1.2122

 AUC_%Extrap(obs.)                  .1165

 Vz(observed)/F                     .9029

 Cl(observed)/F                     .8249

 AUCINF(predicted)               363.6438

 AUCINF(predicted)/D               1.2121

 AUC_%Extrap(pred.)                 .1106

 Vz(predicted)/F                    .9030

 Cl(predicted)/F                    .8250

 AUMClast                       1270.7918

 AUMCINF(observed)              1275.4915

 AUMC_%Extrap(obs.)                 .3685

 AUMCINF(predicted)             1275.2520

 AUMC_%Extrap(pred.)                .3497

 MRTlast                           3.4985

 MRTINF(observed)                  3.5073

 MRTINF(predicted)                 3.5069

 NORMAL ENDING



Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Male

Start Time: 20:22:02 07-26-2013

End Time:   20:22:03 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

TITLE 1

DIPE inhalation 3600 ppm

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 5

DTIME 0

NCONSTANTS 1

CONSTANTS 300

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 14

DATA 'WINNLIN.DAT'

BEGIN

DIPE inhalation 3600 ppm

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .8330E-01     19.30                            .8038      .6695E-01

  .1670         25.21                            2.667      .3104

  .2500         31.75                            5.031      .8146

  .5000         37.95                            13.74      4.179

  1.000         44.55                            34.37      20.06

  2.000         48.72                            81.01      91.06

  4.000         55.71                            185.4      411.3

  6.000         47.56                            288.7      919.5

  6.250         17.94                            296.9      969.2

  6.500         10.34                            300.4      991.6

  7.000         7.899                            305.0      1022.

  7.330     *   3.841      3.765      .7544E-01  306.9      1036.     
1.000

  8.000     *   2.209      2.268     -.5928E-01  308.9      1051.     
1.000

  10.00     *   .5031      .4998      .3333E-02  311.7      1074.     
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .9995

 Rsq(adjusted)                      .9990

 Corr(x:y)                         -.9997

 Tlag                               .0000

 Tmax                              4.0000

 Cmax                             55.7082

 No._points_Lambda_z                3

 Tlast                            10.0000

 Clast                              .5031

 AUClast                         311.6541

 Lambda_z                           .7563

 Lambda_z_lower                    7.3300

 Lambda_z_upper                   10.0000

 t1/2_Lambda_z                      .9165

 AUCall                          311.6541

 AUCINF(observed)                312.3194

 AUCINF(observed)/D                1.0411

 AUC_%Extrap(obs.)                  .2130

 Vz(observed)/F                    1.2701

 Cl(observed)/F                     .9606

 AUCINF(predicted)               312.3150

 AUCINF(predicted)/D               1.0410

 AUC_%Extrap(pred.)                 .2116

 Vz(predicted)/F                   1.2701

 Cl(predicted)/F                    .9606

 AUMClast                       1074.0417

 AUMCINF(observed)              1081.5742

 AUMC_%Extrap(obs.)                 .6964

 AUMCINF(predicted)             1081.5243

 AUMC_%Extrap(pred.)                .6919

 MRTlast                           3.4463

 MRTINF(observed)                  3.4630

 MRTINF(predicted)                 3.4629

 NORMAL ENDING

Input File: Workbook - [Untitled1]

Sex=Female

                                                  Date:   10/16/2011

                                                  Time:     21:26:08

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   14

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

    0.08330        20.22                           0.8421    0.07015

     0.1670        29.69                            2.931     0.3482

     0.2500        31.60                            5.474     0.8818

     0.5000        42.05                            14.68      4.497

      1.000        47.61                            37.09      21.66

      2.000        60.34                            91.07      105.8

      4.000        60.56                            212.0      468.7

      6.000        65.61                            338.1      1105.

      6.250        18.67                            348.7      1168.

      6.500        12.06                            352.5      1193.

      7.000 *      6.130      5.693     0.4370      357.1      1223.    
 1.000

      7.330 *      4.409      4.211     0.1971      358.8      1236.    
 1.000

      8.000 *      1.923      2.283    -0.3608      360.9      1252.    
 1.000

      10.00 *     0.3870     0.3673    0.01972      363.2      1271.    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.9913

Rsq_adjusted                                              0.9869

Corr_XY                                                  -0.9956

No_points_lambda_z                                        4

Lambda_z                               1/hr               0.9136

Lambda_z_lower                           hr               7.0000

Lambda_z_upper                           hr              10.0000

HL_Lambda_z                              hr               0.7587

Tlag                                     hr               0.0000

Tmax                                     hr               6.0000

Cmax                                  ug/mL              65.6099

Cmax_D                          kg*ug/mL/mg               0.2187

Tlast                                    hr              10.0000

Clast                                 ug/mL               0.3870

AUClast                            hr*ug/mL             363.2418

AUCall                             hr*ug/mL             363.2418

AUCINF_obs                         hr*ug/mL             363.6654

AUCINF_D_obs                 hr*kg*ug/mL/mg               1.2122

AUC_%Extrap_obs                           %               0.1165

Vz_F_obs                              mL/kg             902.9195

Cl_F_obs                           mL/hr/kg             824.9342

AUCINF_pred                        hr*ug/mL             363.6438

AUCINF_D_pred                hr*kg*ug/mL/mg               1.2121

AUC_%Extrap_pred                          %               0.1106

Vz_F_pred                             mL/kg             902.9731

Cl_F_pred                          mL/hr/kg             824.9831

AUMClast                        hr*hr*ug/mL            1270.7918

AUMCINF_obs                     hr*hr*ug/mL            1275.4915

AUMC_%Extrap_obs                          %               0.3685

AUMCINF_pred                    hr*hr*ug/mL            1275.2520

AUMC_%Extrap_pred                         %               0.3497

MRTlast                                  hr               3.4985

MRTINF_obs                               hr               3.5073

MRTINF_pred                              hr               3.5069

Input File: Workbook - [Untitled1]

Sex=Male

                                                  Date:   10/16/2011

                                                  Time:     21:26:08

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   14

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

    0.08330        19.30                           0.8038    0.06695

     0.1670        25.21                            2.667     0.3104

     0.2500        31.75                            5.031     0.8146

     0.5000        37.95                            13.74      4.179

      1.000        44.55                            34.37      20.06

      2.000        48.72                            81.01      91.06

      4.000        55.71                            185.4      411.3

      6.000        47.56                            288.7      919.5

      6.250        17.94                            296.9      969.2

      6.500        10.34                            300.4      991.6

      7.000        7.899                            305.0      1022.

      7.330 *      3.841      3.765    0.07544      306.9      1036.    
 1.000

      8.000 *      2.209      2.268   -0.05928      308.9      1051.    
 1.000

      10.00 *     0.5031     0.4998   0.003333      311.7      1074.    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.9995

Rsq_adjusted                                              0.9990

Corr_XY                                                  -0.9997

No_points_lambda_z                                        3

Lambda_z                               1/hr               0.7563

Lambda_z_lower                           hr               7.3300

Lambda_z_upper                           hr              10.0000

HL_Lambda_z                              hr               0.9165

Tlag                                     hr               0.0000

Tmax                                     hr               4.0000

Cmax                                  ug/mL              55.7082

Cmax_D                          kg*ug/mL/mg               0.1857

Tlast                                    hr              10.0000

Clast                                 ug/mL               0.5031

AUClast                            hr*ug/mL             311.6541

AUCall                             hr*ug/mL             311.6541

AUCINF_obs                         hr*ug/mL             312.3194

AUCINF_D_obs                 hr*kg*ug/mL/mg               1.0411

AUC_%Extrap_obs                           %               0.2130

Vz_F_obs                              mL/kg            1270.0912

Cl_F_obs                           mL/hr/kg             960.5552

AUCINF_pred                        hr*ug/mL             312.3150

AUCINF_D_pred                hr*kg*ug/mL/mg               1.0410

AUC_%Extrap_pred                          %               0.2116

Vz_F_pred                             mL/kg            1270.1091

Cl_F_pred                          mL/hr/kg             960.5687

AUMClast                        hr*hr*ug/mL            1074.0417

AUMCINF_obs                     hr*hr*ug/mL            1081.5742

AUMC_%Extrap_obs                          %               0.6964

AUMCINF_pred                    hr*hr*ug/mL            1081.5243

AUMC_%Extrap_pred                         %               0.6919

MRTlast                                  hr               3.4463

MRTINF_obs                               hr               3.4630

MRTINF_pred                              hr               3.4629

Kinetics of Isopropanol in Male and Female Rats exposed to 3600 ppm
DIPE by inhalation.

Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Female

Start Time: 20:20:27 07-26-2013

End Time:   20:20:28 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 4

DTIME 0

NCONSTANTS 1

CONSTANTS 300

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 11

DATA 'WINNLIN.DAT'

BEGIN



 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .5000         3.329                            .8323      .4162

  1.000         5.146                            2.951      2.119

  2.000         10.75                            10.90      15.44

  4.000         21.48                            43.13      122.9

  6.000         31.61                            96.21      398.4

  6.250         35.71                            104.6      450.0

  6.500         25.59                            112.3      498.7

  7.000         25.37                            125.0      584.7

  7.330     *   15.16      16.02     -.8632      131.7      632.3     
1.000

  8.000     *   11.81      10.97      .8418      140.8      701.2     
1.000

  10.00     *   3.477      3.542     -.6510E-01  156.0      830.5     
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .9929

 Rsq(adjusted)                      .9857

 Corr(x:y)                         -.9964

 Tlag                               .0000

 Tmax                              6.2500

 Cmax                             35.7084

 No._points_Lambda_z                3

 Tlast                            10.0000

 Clast                             3.4767

 AUClast                         156.0429

 Lambda_z                           .5653

 Lambda_z_lower                    7.3300

 Lambda_z_upper                   10.0000

 t1/2_Lambda_z                     1.2261

 AUCall                          156.0429

 AUCINF(observed)                162.1929

 AUCINF(observed)/D                 .5406

 AUC_%Extrap(obs.)                 3.7918

 Vz(observed)/F                    3.2718

 Cl(observed)/F                    1.8496

 AUCINF(predicted)               162.3080

 AUCINF(predicted)/D                .5410

 AUC_%Extrap(pred.)                3.8600

 Vz(predicted)/F                   3.2695

 Cl(predicted)/F                   1.8483

 AUMClast                        830.4762

 AUMCINF(observed)               902.8544

 AUMC_%Extrap(obs.)                8.0166

 AUMCINF(predicted)              904.2096

 AUMC_%Extrap(pred.)               8.1545

 MRTlast                           5.3221

 MRTINF(observed)                  5.5665

 MRTINF(predicted)                 5.5709

 NORMAL ENDING



Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Male

Start Time: 20:20:29 07-26-2013

End Time:   20:20:30 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 4

DTIME 0

NCONSTANTS 1

CONSTANTS 300

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 13

DATA 'WINNLIN.DAT'

BEGIN



 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .1670         2.655                            .2217      .3702E-01

  .2500         3.340                            .4705      .9008E-01

  .5000         5.876                            1.623      .5617

  1.000         11.66                            6.008      4.212

  2.000         22.37                            23.02      32.41

  4.000         42.30                            87.69      246.4

  6.000         66.18                            196.2      812.7

  6.250         63.39                            212.4      911.8

  6.500         63.39                            228.2      1013.

  7.000         50.95                            256.8      1205.

  7.330     *   43.93      45.46     -1.528      272.5      1317.     
1.000

  8.000     *   31.88      30.46      1.423      297.9      1510.     
1.000

  10.00     *   9.113      9.218     -.1050      338.9      1857.     
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .9976

 Rsq(adjusted)                      .9951

 Corr(x:y)                         -.9988

 Tlag                               .0000

 Tmax                              6.0000

 Cmax                             66.1823

 No._points_Lambda_z                3

 Tlast                            10.0000

 Clast                             9.1135

 AUClast                         338.8580

 Lambda_z                           .5976

 Lambda_z_lower                    7.3300

 Lambda_z_upper                   10.0000

 t1/2_Lambda_z                     1.1598

 AUCall                          338.8580

 AUCINF(observed)                354.1077

 AUCINF(observed)/D                1.1804

 AUC_%Extrap(obs.)                 4.3065

 Vz(observed)/F                    1.4176

 Cl(observed)/F                     .8472

 AUCINF(predicted)               354.2833

 AUCINF(predicted)/D               1.1809

 AUC_%Extrap(pred.)                4.3539

 Vz(predicted)/F                   1.4169

 Cl(predicted)/F                    .8468

 AUMClast                       1856.5314

 AUMCINF(observed)              2034.5451

 AUMC_%Extrap(obs.)                8.7496

 AUMCINF(predicted)             2036.5957

 AUMC_%Extrap(pred.)               8.8414

 MRTlast                           5.4788

 MRTINF(observed)                  5.7456

 MRTINF(predicted)                 5.7485

 NORMAL ENDING

Input File: Workbook - [C:\Documen...\DIPE Pilot_705548.pwo]

Sex=Female

                                                  Date:    3/25/2013

                                                  Time:     10:12:54

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   11

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

     0.5000        3.329                           0.8323     0.4162

      1.000        5.146                            2.951      2.119

      2.000        10.75                            10.90      15.44

      4.000        21.48                            43.13      122.9

      6.000        31.61                            96.21      398.4

      6.250        35.71                            104.6      450.0

      6.500        25.59                            112.3      498.7

      7.000        25.37                            125.0      584.7

      7.330 *      15.16      16.02    -0.8632      131.7      632.3    
 1.000

      8.000 *      11.81      10.97     0.8418      140.8      701.2    
 1.000

      10.00 *      3.477      3.542   -0.06510      156.0      830.5    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.9929

Rsq_adjusted                                              0.9857

Corr_XY                                                  -0.9964

No_points_lambda_z                                        3

Lambda_z                               1/hr               0.5653

Lambda_z_lower                           hr               7.3300

Lambda_z_upper                           hr              10.0000

HL_Lambda_z                              hr               1.2261

Tlag                                     hr               0.0000

Tmax                                     hr               6.2500

Cmax                                  ug/mL              35.7084

Cmax_D                          kg*ug/mL/mg               0.1190

Tlast                                    hr              10.0000

Clast                                 ug/mL               3.4767

AUClast                            hr*ug/mL             156.0429

AUCall                             hr*ug/mL             156.0429

AUCINF_obs                         hr*ug/mL             162.1929

AUCINF_D_obs                 hr*kg*ug/mL/mg               0.5406

AUC_%Extrap_obs                           %               3.7918

Vz_F_obs                              mL/kg            3271.8418

Cl_F_obs                           mL/hr/kg            1849.6498

AUCINF_pred                        hr*ug/mL             162.3080

AUCINF_D_pred                hr*kg*ug/mL/mg               0.5410

AUC_%Extrap_pred                          %               3.8600

Vz_F_pred                             mL/kg            3269.5205

Cl_F_pred                          mL/hr/kg            1848.3375

AUMClast                        hr*hr*ug/mL             830.4762

AUMCINF_obs                     hr*hr*ug/mL             902.8543

AUMC_%Extrap_obs                          %               8.0166

AUMCINF_pred                    hr*hr*ug/mL             904.2096

AUMC_%Extrap_pred                         %               8.1545

MRTlast                                  hr               5.3221

MRTINF_obs                               hr               5.5665

MRTINF_pred                              hr               5.5709



Input File: Workbook - [C:\Documen...\DIPE Pilot_705548.pwo]

Sex=Male

                                                  Date:    3/25/2013

                                                  Time:     10:12:55

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   13

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

     0.1670        2.655                           0.2217    0.03702

     0.2500        3.340                           0.4705    0.09008

     0.5000        5.876                            1.623     0.5617

      1.000        11.66                            6.008      4.212

      2.000        22.37                            23.02      32.41

      4.000        42.30                            87.69      246.4

      6.000        66.18                            196.2      812.7

      6.250        63.39                            212.4      911.8

      6.500        63.39                            228.2      1013.

      7.000        50.95                            256.8      1205.

      7.330 *      43.93      45.46     -1.528      272.5      1317.    
 1.000

      8.000 *      31.88      30.46      1.423      297.9      1510.    
 1.000

      10.00 *      9.113      9.218    -0.1050      338.9      1857.    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.9976

Rsq_adjusted                                              0.9951

Corr_XY                                                  -0.9988

No_points_lambda_z                                        3

Lambda_z                               1/hr               0.5976

Lambda_z_lower                           hr               7.3300

Lambda_z_upper                           hr              10.0000

HL_Lambda_z                              hr               1.1598

Tlag                                     hr               0.0000

Tmax                                     hr               6.0000

Cmax                                  ug/mL              66.1823

Cmax_D                          kg*ug/mL/mg               0.2206

Tlast                                    hr              10.0000

Clast                                 ug/mL               9.1135

AUClast                            hr*ug/mL             338.8580

AUCall                             hr*ug/mL             338.8580

AUCINF_obs                         hr*ug/mL             354.1077

AUCINF_D_obs                 hr*kg*ug/mL/mg               1.1804

AUC_%Extrap_obs                           %               4.3065

Vz_F_obs                              mL/kg            1417.6234

Cl_F_obs                           mL/hr/kg             847.1999

AUCINF_pred                        hr*ug/mL             354.2833

AUCINF_D_pred                hr*kg*ug/mL/mg               1.1809

AUC_%Extrap_pred                          %               4.3539

Vz_F_pred                             mL/kg            1416.9205

Cl_F_pred                          mL/hr/kg             846.7799

AUMClast                        hr*hr*ug/mL            1856.5314

AUMCINF_obs                     hr*hr*ug/mL            2034.5451

AUMC_%Extrap_obs                          %               8.7496

AUMCINF_pred                    hr*hr*ug/mL            2036.5957

AUMC_%Extrap_pred                         %               8.8414

MRTlast                                  hr               5.4788

MRTINF_obs                               hr               5.7456

MRTINF_pred                              hr               5.7485

Kinetics of Acetone in Male and Female Rats exposed to 3600 ppm DIPE by
inhalation.

Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Female

Start Time: 20:34:13 07-26-2013

End Time:   20:34:14 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

TITLE 1

ACETONE

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 3

DTIME 0

NCONSTANTS 1

CONSTANTS 0

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 16

DATA 'WINNLIN.DAT'

BEGIN

ACETONE

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .8330E-01     4.313                            .1796      .1496E-01

  .1670         5.011                            .5698      .6502E-01

  .2500         8.525                            1.132      .1882

  .5000         16.78                            4.295      1.503

  1.000         36.05                            17.50      12.61

  2.000         70.83                            70.94      101.5

  4.000         147.5                            289.3      833.3

  6.000     *   209.4      238.2     -28.85      646.2      2680.     
1.000

  6.250     *   211.3      221.2     -9.884      698.8      3002.     
1.000

  6.500     *   190.3      205.4     -15.05      749.0      3322.     
1.000

  7.000     *   208.4      177.1      31.35      848.7      3996.     
1.000

  7.330     *   197.7      160.6      37.13      915.7      4476.     
1.000

  8.000     *   199.7      131.6      68.12      1049.      5496.     
1.000

  10.00     *   115.5      72.72      42.75      1364.      8249.     
1.000

  16.00     *   1.900      12.26     -10.36      1716.      .1180E+05 
1.000

  24.00     *   2.714      1.143      1.572      1735.      .1219E+05 
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .8462

 Rsq(adjusted)                      .8242

 Corr(x:y)                         -.9199

 Tlag                               .0000

 Tmax                              6.2500

 Cmax                            211.3271

 No._points_Lambda_z                9

 Tlast                            24.0000

 Clast                             2.7144

 AUClast                        1734.6584

 Lambda_z                           .2967

 Lambda_z_lower                    6.0000

 Lambda_z_upper                   24.0000

 t1/2_Lambda_z                     2.3365

 AUCall                         1734.6584

 AUCINF(observed)               1743.8079

 AUC_%Extrap(obs.)                  .5247

 Vz(observed)/F                     .0000

 Cl(observed)/F                     .0000

 AUCINF(predicted)              1738.5099

 AUC_%Extrap(pred.)                 .2215

 Vz(predicted)/F                    .0000

 Cl(predicted)/F                    .0000

 AUMClast                      12186.3930

 AUMCINF(observed)             12436.8235

 AUMC_%Extrap(obs.)                2.0136

 AUMCINF(predicted)            12291.8109

 AUMC_%Extrap(pred.)                .8576

 MRTlast                           7.0252

 MRTINF(observed)                  7.1320

 MRTINF(predicted)                 7.0703

 NORMAL ENDING



Input File: Data - [A:\DIPEPK~1.XLS]

Sex=Male

Start Time: 20:34:14 07-26-2013

End Time:   20:34:15 07-26-2013

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)

                          Core Version 29Oct97

 Listing of input commands

TITLE 1

ACETONE

MODEL 200

NVARIABLES 5

NPOINTS 100

XNUMBER 1

YNUMBER 3

DTIME 0

NCONSTANTS 1

CONSTANTS 0

METHOD 2  'Linear trapezoidal

NCATRANS

MISSING 'Missing'

NOBSERVATIONS 16

DATA 'WINNLIN.DAT'

BEGIN

ACETONE

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC     
WEIGHT

 -----------------------------------------------------------------------
-----

  .0000         .0000                            .0000      .0000

  .8330E-01     5.399                            .2249      .1873E-01

  .1670         8.666                            .8135      .9812E-01

  .2500         12.54                            1.694      .2883

  .5000         25.40                            6.437      2.268

  1.000         50.45                            25.40      18.06

  2.000         98.81                            100.0      142.1

  4.000         203.3                            402.2      1153.

  6.000         288.4                            893.9      3697.

  6.250         298.9                            967.3      4147.

  6.500         319.4                            1045.      4640.

  7.000     *   312.5      434.3     -121.8      1203.      5705.     
1.000

  7.330     *   315.1      393.3     -78.20      1306.      6447.     
1.000

  8.000     *   301.9      321.7     -19.86      1513.      8030.     
1.000

  10.00     *   230.1      176.6      53.50      2045.      .1275E+05 
1.000

  16.00     *   66.65      29.19      37.46      2935.      .2285E+05 
1.000

  24.00     *   1.646      2.649     -1.003      3208.      .2727E+05 
1.000

 -----------------------------------------------------------------------
-----

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for
extrapolation purposes

 Dosing_time                        .0000

 Rsq                                .9471

 Rsq(adjusted)                      .9339

 Corr(x:y)                         -.9732

 Tlag                               .0000

 Tmax                              6.5000

 Cmax                            319.3774

 No._points_Lambda_z                6

 Tlast                            24.0000

 Clast                             1.6460

 AUClast                        3208.0971

 Lambda_z                           .3000

 Lambda_z_lower                    7.0000

 Lambda_z_upper                   24.0000

 t1/2_Lambda_z                     2.3107

 AUCall                         3208.0971

 AUCINF(observed)               3213.5841

 AUC_%Extrap(obs.)                  .1707

 Vz(observed)/F                     .0000

 Cl(observed)/F                     .0000

 AUCINF(predicted)              3216.9267

 AUC_%Extrap(pred.)                 .2745

 Vz(predicted)/F                    .0000

 Cl(predicted)/F                    .0000

 AUMClast                      27270.9342

 AUMCINF(observed)             27420.9130

 AUMC_%Extrap(obs.)                 .5470

 AUMCINF(predicted)            27512.2765

 AUMC_%Extrap(pred.)                .8772

 MRTlast                           8.5007

 MRTINF(observed)                  8.5328

 MRTINF(predicted)                 8.5523

 NORMAL ENDING

Input File: Workbook - [C:\Documen...\DIPE Pilot_705548.pwo]

Sex=Female

                                                  Date:   10/16/2011

                                                  Time:     21:35:09

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   16

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

    0.08330        4.313                           0.1796    0.01496

     0.1670        5.011                           0.5698    0.06502

     0.2500        8.525                            1.132     0.1882

     0.5000        16.78                            4.295      1.503

      1.000        36.05                            17.50      12.61

      2.000        70.83                            70.94      101.5

      4.000        147.5                            289.3      833.3

      6.000        209.4                            646.2      2680.

      6.250 *      211.3      227.0     -15.63      698.8      3002.    
 1.000

      6.500 *      190.3      210.6     -20.28      749.0      3322.    
 1.000

      7.000 *      208.4      181.4      27.04      848.7      3996.    
 1.000

      7.330 *      197.7      164.4      33.34      915.7      4476.    
 1.000

      8.000 *      199.7      134.5      65.21      1049.      5496.    
 1.000

      10.00 *      115.5      74.01      41.46      1364.      8249.    
 1.000

      16.00 *      1.900      12.32     -10.42      1716. 1.180e+004    
 1.000

      24.00 *      2.714      1.128      1.586      1735. 1.219e+004    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.8398

Rsq_adjusted                                              0.8131

Corr_XY                                                  -0.9164

No_points_lambda_z                                        8

Lambda_z                               1/hr               0.2988

Lambda_z_lower                           hr               6.2500

Lambda_z_upper                           hr              24.0000

HL_Lambda_z                              hr               2.3195

Tlag                                     hr               0.0000

Tmax                                     hr               6.2500

Cmax                                  ug/mL             211.3271

Cmax_D                          kg*ug/mL/mg               0.7044

Tlast                                    hr              24.0000

Clast                                 ug/mL               2.7144

AUClast                            hr*ug/mL            1734.6584

AUCall                             hr*ug/mL            1734.6584

AUCINF_obs                         hr*ug/mL            1743.7414

AUCINF_D_obs                 hr*kg*ug/mL/mg               5.8125

AUC_%Extrap_obs                           %               0.5209

Vz_F_obs                              mL/kg             575.7073

Cl_F_obs                           mL/hr/kg             172.0439

AUCINF_pred                        hr*ug/mL            1738.4328

AUCINF_D_pred                hr*kg*ug/mL/mg               5.7948

AUC_%Extrap_pred                          %               0.2171

Vz_F_pred                             mL/kg             577.4653

Cl_F_pred                          mL/hr/kg             172.5692

AUMClast                        hr*hr*ug/mL           12186.3930

AUMCINF_obs                     hr*hr*ug/mL           12434.7792

AUMC_%Extrap_obs                          %               1.9975

AUMCINF_pred                    hr*hr*ug/mL           12289.6083

AUMC_%Extrap_pred                         %               0.8399

MRTlast                                  hr               7.0252

MRTINF_obs                               hr               7.1311

MRTINF_pred                              hr               7.0694

Input File: Workbook - [C:\Documen...\DIPE Pilot_705548.pwo]

Sex=Male

                                                  Date:   10/16/2011

                                                  Time:     21:35:09

                  WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

                        Version 5.3  Build 200912111339

                            Core Version 18Sept2006

Settings

--------

Model:  Plasma Data, Extravascular Administration

Number of nonmissing observations:   16

Dose time:      0.00

Dose amount:      300.00

Calculation method:  Linear Trapezoidal with Linear Interpolation

Weighting for lambda_z calculations:  Uniform weighting

Lambda_z method:  Find best fit for lambda_z,  Log regression

Summary Table

-------------

      Time         Conc.      Pred.    Residual      AUC       AUMC     
Weight

         hr       ug/mL       ug/mL       ug/mL    hr*ug/mL hr*hr*ug/mL

------------------------------------------------------------------------
-------

     0.0000 @     0.0000                           0.0000     0.0000

    0.08330        5.399                           0.2249    0.01873

     0.1670        8.666                           0.8135    0.09812

     0.2500        12.54                            1.694     0.2883

     0.5000        25.40                            6.437      2.268

      1.000        50.45                            25.40      18.06

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      2.000        98.81                            100.0      142.1

      4.000        203.3                            402.2      1153.

      6.000        288.4                            893.9      3697.

      6.250        298.9                            967.3      4147.

      6.500        319.4                            1045.      4640.

      7.000 *      312.5      434.3     -121.8      1203.      5705.    
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      7.330 *      315.1      393.3     -78.20      1306.      6447.    
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      8.000 *      301.9      321.7     -19.86      1513.      8030.    
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      10.00 *      230.1      176.6      53.50      2045. 1.275e+004    
 1.000

      16.00 *      66.65      29.19      37.46      2935. 2.285e+004    
 1.000

      24.00 *      1.646      2.649     -1.003      3208. 2.727e+004    
 1.000

@) Note - the concentration at dose time was added for extrapolation
purposes.

*) Starred values were included in the estimation of Lambda_z.

Final Parameters

---------------

Rsq                                                       0.9471

Rsq_adjusted                                              0.9339

Corr_XY                                                  -0.9732

No_points_lambda_z                                        6

Lambda_z                               1/hr               0.3000

Lambda_z_lower                           hr               7.0000

Lambda_z_upper                           hr              24.0000

HL_Lambda_z                              hr               2.3107

Tlag                                     hr               0.0000

Tmax                                     hr               6.5000

Cmax                                  ug/mL             319.3774

Cmax_D                          kg*ug/mL/mg               1.0646

Tlast                                    hr              24.0000

Clast                                 ug/mL               1.6460

AUClast                            hr*ug/mL            3208.0971

AUCall                             hr*ug/mL            3208.0971

AUCINF_obs                         hr*ug/mL            3213.5841

AUCINF_D_obs                 hr*kg*ug/mL/mg              10.7119

AUC_%Extrap_obs                           %               0.1707

Vz_F_obs                              mL/kg             311.2023

Cl_F_obs                           mL/hr/kg              93.3537

AUCINF_pred                        hr*ug/mL            3216.9267

AUCINF_D_pred                hr*kg*ug/mL/mg              10.7231

AUC_%Extrap_pred                          %               0.2745

Vz_F_pred                             mL/kg             310.8790

Cl_F_pred                          mL/hr/kg              93.2567

AUMClast                        hr*hr*ug/mL           27270.9342

AUMCINF_obs                     hr*hr*ug/mL           27420.9130

AUMC_%Extrap_obs                          %               0.5470

AUMCINF_pred                    hr*hr*ug/mL           27512.2766

AUMC_%Extrap_pred                         %               0.8772

MRTlast                                  hr               8.5007

MRTINF_obs                               hr               8.5328

MRTINF_pred                              hr               8.5523

 PAGE   32 

RTI Project No.: 0209408.004	Protocol No. RTI-934	Final Report

RTI Project No.: 0209408.001	Protocol No. RTI-934	Final Report

  PAGE  x 

RTI Project No.: 0209508.001	Protocol No. RTI-934	Final Report

Table of Contents

(continued)

Page

  PAGE  v 

RTI Project No.: 0209408.001	Protocol No. RTI-934	Final Report

  PAGE  21 

  PAGE  22 

  PAGE  36 

RTI Project No.: 0209408.001	Protocol No. RTI-934	Final Report

RTI Project No.: 0209408.001	Protocol No. RTI-934	Final Report

  PAGE  45 

A-  PAGE  1 

A-  PAGE  34 

A -   PAGE  2 

B-  PAGE  12 

B -   PAGE  1 

C-  PAGE  1 

C -   PAGE  2 

D-  PAGE  1 

D-  PAGE  95 

E-  PAGE  17 

F-  PAGE  65 

HG-  PAGE  8 

HH-  PAGE  1 

H -   PAGE  26 

I -   PAGE  27 

J -   PAGE  16 

