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`TRADE SECRET
Study Title 90H--D2a4y67O8r:alSGuabvcahgroenSitcuTdoyxiinciRtayts
Volume 2 of 4
Laboratory Project ID: DuPont-6554
ARRR6 -- 3244
Dupont
PN
||
TEST GUIDELINES: U.S. EPA Health Effects Test Guidelines (OPPTS 870.3100 (1998)
AuTHOR:: Don A.. Delker,Delker, Ph.Ph.] D
STUDY COMPLETED ON: April 22,2002 PERFORMING LABORATORY: E.L du Pont de Nemours and Company
Haskell Laboratory for Health and Environmental Sciences `Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050
WORK REQUEST NomexEE
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~
FIGURES
`Study Design
EXPLANATORY NOTES
DuPon.6554
MalGerouFpemale Dosage
Test Substance
T mW
1 IV
O60mmggkkggddaayy
VIseohpircolpeacnoonltrcoolntrol
V VI
VI VII
6100mmggkkggddaayy
HH2244667788
IX X 300 mgkgday H-24678
Critical Dates:
Day90 > Loanset-mdoanytohfatnesdt 3s-ubmsotnatnhcereacdomvienriystpreartiioodns.for male and female rats designated for the
Day91 > Last day of test substance administration for male rats designated for the 90-day sacrifice.
--_
> Recovery period begins for rats designated for the one-month and 3-month recovery periods.
Day 92
>
Last day of test substance administration for female rats designated for the 90-day sacrifice.
> Male rats designatedforthe 90-day sacrifice were sacrificed.
Day 93 > Female ras designated for the 90-day sacrifice were sacrificed.
Day 122 > Male and female rats designatedforthe one-monthrecoveryperiod were sacrificed.
Statistical Methods for Neurobehavioral Figures
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Dupon6554
APPENDICES
~
--~
- = CompanySanlized. Donotnanisnin TSCA CBI
H9-02-4D6a7y8O:raSlubGcahvraogneicSTotriuciintdRyatys
DuPont655
~~ `Table L Concentration Verification and Stability ofH-24678 in Dosing Solutions
Preparation Day
`mg/mL H-24678(A)
Percent
Sample Type
Nominal Measured
Nominal
Test Day 1
Concentration Verification)
Control
00
ND
--
1331 1332
Mean);
151 148
1.50%0.02
cv.1%
1135 1113
112.8)
800-1
732
915
800-2
199
99.9
Mean); 7.66 0.47
95.8)
CV.6%
4001
404
101.0
4002
368
920
Mean): 38.625
(96.5)
CV.6%
Stability
5-Hour Room Temperature
133
141
1060
7-Day Refrigerated()
133
149
1120
5Hour Room Temperature(E) 133
159
1195
5-Hour Room Temperature
800
7.80
975
7-Day Refrigerated)
8.00
871
108.9
5 Hour Room Temperature(E) 800
863
107.9
5-Hour Room Temperature
400
382
955
7-Day Refrigerated(D)
400
us
1120
C 5 Hoa ur Room Temperature(E) 40.0 7S moi ne43v4ale. FEATS 08.5
Denotes not detced.
Fcc. MeSDa.12ndC,V. clulted to veiy uniformityof mixture.
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oe snai the dy,
| ---
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--
CompanySanitized. Doesnot contain TSCA CBI
9H02.4D6a7y8O:raSlubGcahvraogreicStTuoxdiyciintyRats
DuPont6554
--_ `Table I:(continued) Concentration Verification and Stability of Isopropyl Alcohol in Dosing
Solutions
Preparation Day
`mg/mL Isopropyl Alcohol
Percent
`Sample Type
Nominal Measured
Nominal
Concentration Verification(A) 80-1 871 1089
802
8.68
108.5
Mean: 8700.02
(108.8)
CV.02%
400-18)
780
915
4002
191
99.6
Mean: 7.89 0.12
98.6)
Cv.2%
5 Hour RoStoabmilTietmyperature 80
8.66
1083
7-Day Refiigerated()
80
880
1100
5 Hour Room Temperature(D)
80
9.04
130
--_
5 Hour Room Temperature 40.08)
803
1004
7-Day Refrigerat(ed)
400
7.99
99
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Dupont6554
~
Table I. Concentration Verification of H-24678 in Dosing Solutions
Preparation Day
mg/mL H-24678(A)
Percent
Sample Ty
Test Day 42
Nominal
Measured
Nominal
ConcentratCioonntVreorlification()
00
ND
--
1331
122
917
1332
120
902
Mean: 1212001 Cvi%
010)
800-1
7.56
9.5
8002
162
953
Mean: 7.59 0.04
049)
CV.1%
400-1
416
1040
4002
363
908
Mean: 39.0%3.7
97.5)
CV. 9%
--
Test Day 91
ConcentratCioonntVreorlification(B)
00
ND)
--
133-1
139
1045
1332
133
1000
Mean: 1360.04 (102.3)
CV.3%
800-1
849
8002
1.96
106.1 995
Mean: 823037
(102.9)
CV.5%
C--O 400-1
379
4002
383
948 958
Mean: 38.1%028
953)
R TroE swansCVv.in1e% Tr
Denotes sondeeted.
--
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9H0A.2D46a7y8O:raSluGbacvhavgoenieStTuodxyicintRyas
Dupont6554
--
`Table IL (continued) Concentration Verification of Isopropyl Alcohol in Dosing Solutions
Preparation Day
`mg/mL Isopropyl Alcohol
Percent
Sample Type
Test Day 42 Concentration Verification(A)
Nominal
`Measured
Nominal
80-1
9.20
1150
8.02
9.02
1128
Mean: 9.11+0.13
(113.9)
CV. 1%
400-1)
40.0-2
Mean:
7.59
741
7.50 0.13
C.V.2%
94.9
92.6
(93.8)
Test Day 91
Concentration Verification(A)
80-1
9.31
802
9.64
Mean: 9.48 0.23
--
C.V.2%
40.0-1B)
721
40.0-2 Mean:
135 7.31+0.06 CV. 1%
116.4
120.5
(118.5)
90.9
91.9 (91.4)
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Figure 1
Representative Analytical Calibration Curves
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Figure 1a: Calibration curve (GC) showing linear fit(line)to replicate peak
area measurements (squares) for calibration solutions of
--_
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Figure 1b: Calibration curve (LC/MS - C6-IPA/mixed bis) showing linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-24678 diluted over a concentration
range of 0.0918 to 0.3213 mg/mL.
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.
calibration solutions ofH-24678 diluted over a concentration
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Sanatn or he ed ns
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Representative Analytical Calibration Curve
DuPont6554
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:
Representative Analytical Calibration Curve
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Figure 1g: tCoarleipblriactaitoenpceuarkvear(eLaCm/eMaSs( uremeR nts (sM quarreoI sv)ifnogr clianleiabrraftiiotnine)
solutions of H-24678 diluted over a concentration range of
~
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[I
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--
Figure 2
Representative
hi
Dupone6554
Figure 2a: Representative GC chromatogramof 3.006 mp/mL. isopropyl alcohol analyticalreferencesolution.
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----
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Figure 2 (continued)
Representative HPLC/MS Chromatography Chromatograms
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9H02-4D6a7y8:OraSlubGcahvraogneicStTuoxdiyciityRats
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--~
Figure 2 (continued)
ReprHPe LC/s MSCe hron matot graa phyt Chroi matv ogre ams
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Figure 2f: RepresentativeHPLC/MS chromatograms of 1.33 mg/mL dosing
|
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|
H-24678. The measured concentration of the representative solution
~~
is 1.51 mg/mL.
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--
|
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H9-02-4D6a7y8:OrSaulbGelaivoangiecSTtoxyiciitnyRats
Dupont6554
APPENDIX B
INDIVDOISEDVOULUAMELS
--~
| |
--_
|
-- m Company Sanhtia zed. Doesnotcolaln TSCA
H902.4D6a7y8O:raSlubGcahvraogneicStTuordiyciintyRats
~~
INDIVIDUAL DOSE VOLUMES
Study Design
EXPLANATORY NOTES
DuPon.6554
MaleGrouFpemale
Dosage
I TT Omgkgday Vehicle control
mM IV 60mgkgday Isopropanol control
V VI 10mgkgday H-24678
VI VII 60mg/kgday H24678
XX 300 day H-24678
Critical Dates
Day90 > Last day of test substance administration for male and female rats designated for the one-month and 3-month recovery periods.
Day91 > Last day of test substance administration for male rats designated for the 90-day exposure period.
--_
> Recovery period begins for rats designated for the one-month and 3-month recovery
periods.
Day92 > Last day of test substance administration for female rats designated for the 90-day exposure period.
> Male rats designated for the 90-day exposure period were sacrificed.
> Male rats dosed with isopropanol (Group IIT) were sacrificed.
Day93 > Femaleratsdesignated for the 90-day exposure period were sacrificed.
> Female rats dosed with isopropanol (Group IV) were sacrificed.
Day 122 > Male and female rats designatedforthe one-month recovery period were sacrificed.
Day 183 > Male and female rats designated for the 3-month recovery period were sacrificed.
Note Unless footnoted, absent data indicates animal was not alive at the time of dosing.
Footnotes a. In error, animal dosed with 60 mg/kg/day isopropanol dose solution. b. Animal may have been misdosed.
8
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