Document O1LRN1QM2614jngv6q6gRazv1
905 Sheehy Drive, Bldg. A Horsham, PA 19044
Telephone: (215) 443-8710
Telefax: (215)443-8587
M S-
II2 V -
ARGUS RESEARCH
Charles River Laboratories
Discovery and Development Services
September 11, 2002
John Butenhoff, Ph.D., DABT, CIH 3M Corporate Toxicology 3M Medical Department 3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000
Telephone: (651) 733-1962
Telefax:
(651) 733-1773
RE: Protocol 418-020 - Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO) in Rats Sponsor's Study Number: T-6889.6
Dear Dr. Butenhoff:
Enclosed are the copies of the estrous cycle evaluation for P and FI generation rats which you requested.
If you have any questions, please do not hesitate to contact me.
Sincerely, Study Coordinator
rCoT3 O
--i
!
ro
Enc.
co cn vD
000003
002947a.
ESTROUS CYCLE EVALUATION P GENERATION FEMALE RATS
000004
EXACT COPY
0 0 3 ^^7
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020
APFO
Estrous Cycle Evaluation
DOSAGE:
GENERATION: ROUTE:
SPECIES/STRAIN:
0 (Vehicle) MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
DATE
i- io l M O I l-3-ei \M \ tf-ol /-VO1
i -j * t ' -5-01 .iO.O> \w\ (//Jo/ i-iv a N to j
1 2 3 4 5 6 7 8 9 10 11 12 13 14
ac
Saline Pre-Check Tech/Time
112,3
a ie oJc oJ?c \\2Xp I6 l a o
//33
TS Ilio
*/
xOiT-
li W3
llfl
^\\b
0\A
II33 V
piA u3i
CtPc o J c aJDc_
Saline PostCheck Tech/Time
12,00
(|55
ib Tb l^o6> i K 1 U5*>
II 12CO
sW piA (Ka
p /2 I^ IZC3 \iS ^ I V ^
Smears Taken fct/Wyvc
Tech/Time Start "$0 1(31
tic/ put
iL tiW a iW
Il V f
4uCp^* liZ/S
cm-*"10 ll 3^
/
m
Mift&tftlfrgy. iU(# nil?
.-vilHzO*
HAiC
IDb
crH*3uihisud7
Smears Taken
Time End an 1157. US'S i \ 5 i
l<% 11*11 US! U 5
i<?n to o im iT ilS
Smears Read
aie oJ>c_ C& jkA W 3
Tech/Time Start IXOt U55 12X
UOi.
Kf i/*n
IZl 115^ 5CI
?p3 Tt %
StH pv4 -^>A ric z XlHi, \xf2>
Smears Read
Time End \m> ILM5 i < 5 31 i3zS
1230 a 3D l^o ( D m i9 \\
Animal Number
13801 13802
b b br
WP bb
f nn b
b b
?s 6b
/H D OP
13803 13804 13805 13806
(VA b
b
p (W NA V PA b <
bb
P
&
E
p
Al p
Mb
D>
Db ?
DD
? fr M p p
fr jm rvv b 7$ b 0
13807
b
13808
13809 13810
P
13811
b
13812
p
Reviewed By:
b P b
T> b
yp
E
? P ~D
E& M ftl ;__
? , E
9
e
b
Pt
V)
bf
A\ b
P
b p - r n
& b J I_ p
E on b b O
Date:
0Sl:dLQ l^^a- 13-Uia r* A ie 5 |:duA 1 3 * 1 3 - 13 43TC
`h iv @/&'l'tloI ^C
VI
bb
Dp
bb
0 <1 C
0
D
_nJ Q
P
/4 o O
P
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W *,-,
OOOOOS
u?I,
<K&^`l^ v
11rtoIo|i /fcf
002948
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
0 (Vehicle) MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus D = Diestrus
DATE
l-l-bl WxA
V*i|oI Il f-o'
IVO 1A.01 i-ti.lJI
I H>0l m-*
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
13813
KV\ b
P? aA P ? e m D
A7
13814 13815
T> T> p
b IVA b
?. |Y1 ? f a IT)
p e /A D ? p
P **
V> T4 o
13816
0b b nrt
E' m
P OTj o T>
13817 13818 13819 13820 13821
zINA b p
IT P & T> _ h _ _ L E D
Pb P 9 (V\ V m b b
0
Vb P
P i> p
V
pa D P
p bA >
p E /A
?F
PM P
1
p A6 > b
PP p
_ b _ b _
13822
c ?IV \ b>
aA P P i> _ _ P
D
13823 13824
B (V\ b
Gb
) aA P f m
P 1 D
9 aA
p m b f.
n
13825 13826
wb P
m &? ? P
P? INA T>
fci
b
. ?
P f - lb
mO
D
p
13827 13828 13829 13830
B b? P IW \>
b b t> b ?
c aA
P
P
P
9 A* AA
D
P g \>
p O
D P jvL b
.
D P M o P
P S D i> D
/I
AJcM -o ]
il*A o \ Reviewed By:
fli-w im a .
Date:
/ RT 01.14.00 EC2-04b
000006
iEXACT COPY I *}} Rlulo>
002949
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
AP FO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
1 MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estais
M = Metestois
D = Diestrus DATE
H-ol (-7 Dl \0-oi 123
i-iol 45
6
l-t-Ol i-9-' |.1-OI IU-I l-iai I-&4I ni-* 7 8 9 10 11 12 13 14
Animal Number
13831 13832 13833 13834 13835 13836 13837 13838
bb
B
e- b b
ff\ D D E /v\
b
D
b %*
pn b D
O
D
D
b 9 m O?
mb ?
eD
VP
m PP B
i> P % - K m b
t> XD P
b EB b
Pf T b b
&b D F
PP B b
T) f F F M
b
p?
B b b > F w b ?
fit\ V L
P ~b
t /A b P
P
0 D
13839 13840
b P B Ai D P F o\ P P B
OO
Pb m b t F
P I v> b
13841 13842 13843 13844
G AA
D P > ?
MP
v>
&b
P0 F P b ? i
b>P
c P P F. '
3> D
O
b ?r
L
? B h\ b
P
aA b
b Dc
13845 13846 13847 13848 13849
E Bb b ?
PbP9
M bO
9N \ b e b O V F m b
TT D O
P Eb
b > b n?
PG Db
/A P D
b P , t>0 b L
m & P
O
bb
P
J? f
b9 (S X 3 )3 1 >
BDO 16|6\
Reviewed By: CT
_________M 7V 0}
^ Ml-oi
Date: - ( . !
S RT 01.14.00 EC2-04
w fte jm
000007
fl i w * 1 " H m t/7M
002950
PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Animal Number 13850 13851 13852 13853 13854 13855 13856 13857 13858 13859 13860
Argus
TEST ARTICLE/SUBSTANCE:
APFO GENERATION: P
ROUTE: Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
Mol llo l 12
3
l>6*o| 456
i '*0 <*<=1 l 0 | -i i i l-tt-61 \i}0\ M-o
7 8 9 10 11 12 13 14
b E b T?
Pb
f .
b D
b E
b f On b b
D
b G (V\ 'D
cT i )
P
w b D
P G "b "D
aa P p
Mb
OC
E b T> s fr P b
P
Dr*\ \>
T>
f\A ~D P c
Pb
P G ISA
P M t>
P P
b b \ D L
Mb P 1
b(
"b
b
04 'T. D
P ET r< f n D F,
c 1W D
b-
u,t >
b
KA b
,V\ D f
t> b
P
b b p 6 /w ,P p F , t) b P L
Q & X & H z i 003Tb Reviewed By:______ _____________ Hfl . HflaL -
Date:
000008
l-lS'fPI
RT 01.14.00 EC2-04b
EXACT COPY
002951
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
3MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus DATE
A/-0/ i-2o( l i o l 12 3
/ Soi AV| KHI l-Y-Oi 1-401 1.1001 / 'M j.<A.o\
l-IS-ol
4 5 6 7 8 9 10 11 12 13 14
Animal Number
13861 13862 13863 13864
Ee M
b BE
b b^
bfE
eb
P
N\ b
D
13865 13866 13867 13868 13869 13870 13871 13872 13873 13874 13875 13876 13877 13878
PB b
P
GL B hA > D
bb
PPc
& NA b
fc
Bb b
> c
?F b b P
i> P 't B IA b
PH D b
E b b P ?
!> B E b 0
?B eB
bb na. b
& IVA b b
c 0 Z
mb
PE
b
13879 Q )(g5Bl|5]0'
b _b_ b
? E r? b P E r> Q
9 P ? . T> b P e
0
? E t>
t bB
f t t> P P t
DD
et AA b
a
u
bB
?
E Ebb
pB
O _
m/A P
/VA P
b ?
e- D
e
D (ESl .
b il
XL
/* P
b __ m
b _ b _ L A
E p t P S ... JH T? P C ,
?EmD
P L D p
D D b L b T> X l 1 X L
P JP 0 e T> b b
O
DP E r . P b F
c P D p E M W B x_
E P > ? _ i J L b O .
9M P
f _ b _ > X __ E -
P E F , rn _D__ P f
E) X L
E /A J D _ P &
M jL
1
Reviewed By:_____ ____________ 'f t t . 'n t L -
Date:__________ _________________ RT 01.14.00 EC2-04b
000009
exact copy
002952
PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Animal Number 13880 13881 13882 13883 13884 13885 13886 13887 13888 13889 13890
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cri:CD (SD) IGS BR VAF/Plus
//d IZ o V V
i
12 34 5
|->` i I' .i t -S.I M00I l-ll-Df l.it-Oi H M
6 7 8 9 10 11 12 13 14
?
bb
V
M t>
P T m
DP
e
D b E E iP ID
mb
DB
mb
Bw
T'A
PE
yv\ D ? E o n p
e E DO
C |M O
Pb b
? E- P
E i > D JD
t> i> V . D
B F,
E f. E E
eE
<r
t> ?. 6 /\A S E
e
t f . 1
eb fn
"b (
b t>
&D
-r' Dt
V pE T7 P ?
m
?C O
T> -- J c .
e B tA b
Pb
P b b >> P E
eb
4$ c b f P fr r> T> b
r `Hi&t
Reviewed By:___________________ M , / M a ^ _____ Date:________ __________ ;_________
RT 01.14.00 EC2-04
O O O O IO
, -F tUuLor
002953
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE: 10 MKD
APFO GENERATION: P
ROUTE: Oral (Gavage)
Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cri:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestms
D = Diestrus
DATE
/-/-cl i-2-ot 1-3*1 H
i"?' 1"i-o* 1-9-ti 1-IOOi i-ll-DI l--CV \-fyoi l-W-ai
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
13891 13892
V\ b b b
e 5 D b e c*-* b b
P ?
m b P A - V D A]
13893
E INA V P [> b T> E b D O C
13894 13895
b EmD
D b b T > -p O
75 E E fn 0 D f m _D_
Emo D
13896 13897
s b b F . b 5 b b > b b
D P J2_ H - p b > _ p
13898
*? E IVA b P B b b ? e JU_ b XD i l
13899 13900
D !>
P
?
e E
nn
O eyr*
f /A ,p
b p
P E
m DO E f i rt--b'
13901 13902
m "b P E (VI f # p f , P b m D D
? E T) D p E m
P & nn t) P
13903
ra b 0 n p f . p b p s y D
13904 13905 13906 13907
mb
~D P b eE
E. xf. ^ 1 0 p r> r . (P p
E m0p n m
b D c r b m
b )) P T - T T ?
m
p bp O b r> p . P b D P i> b
13908 13909
~P e
Eb
*A b b
? B b > p
D _D_
E
D
b D _ J k _
P P 1 D
Reviewed By:_____ _______________ ' M . j k L
_ Date:
1 - & 01________________
RT 01.14.00 EC2-04
O O O O ll
4
r\
002954
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
10 MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
DATE
H-oi 12-01 1*3-01 HIox J.&oi H w f-T-oi l--v i-'i-l 1-lfcCl
v(y0\ hH-a
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number 13910
9 eb
13911 13912 13913
es. tvs b D b
r\ b p
b b Z
13914 13915 13916 13917 13918 13919 13920
bb eb
"D b eB
Eb rw b
b
eF b? B
ISA b bP Pf
bL
Db Dt D
OP
e 1* b
pP
B0
fV\ p
P
mb b bL b
F bb
O r->
b t) D P v> b
P X) D
bb D D > O t> P 1.
G
& p F. b P e
P (T) > e z -D O
b b P f. M
P IL
P P b b P - O
P D t> T>
D
t m P p,
nD
Reviewed By:________________ %
_______ Date:_______ ( .01______________
RT 01.14.00 EC2-04b
000012
EXACT COPY ^luUi-
002955
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
30 MKD P = Proestrus
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
E = Estrus
M = Metestrus
D = Diestrus DATE
t-i-o1 Moi '3-ol h\
12345
i-Y-Ol
1-1ot /I6-0I (n-i |./a-oi HV )
6 7 8 9 10 11 12 13 14
Animal Number
13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932
"D b B D
~) B X)
E
V
y E T> TD
E (VA
?
"D B Cri
D PE m
"P B (NA b
P fi
D P e PT) e b ~b P
D "b P
13933
B
13934 13935 13936
e "b N <
E B NA
E b
13937
!D
13938 13939
D __
GfW H U I
e
e
Z ' B T? EV
bf
D
PF PF
n Df Df Df
P E
Dp
B IA
|W h cn
Dp Ch
bp bf
bP
f . "D b hb m 1)
? tm
Em
h t> h (Tl eD
bf
b
pZ b?
Eb rp
)f
E6
HD
s*
O T> E
b T>
f EV
p A/1
m
r> ? ?
E
B
6
b nn b?
E
s*
tm T> D nn b b
1b
D B V
Df i
b> p
b> T> by* T> ?
JL_ 6
DO
D X) > p DP ? mO nn O
bO mD
pE
e /I
t-
_ m -to
>
D
P Ab J _ Xb
F ?
o
n p
C-
JD -D D *
D
1T
O 0 T> O
Reviewed By:____________________ M
_____ Date:____ t i S M ________________
RT 01.14.00 EC2-04b
000013
t
002956
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
30 MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus DATE
l-l-ol \-lo\
12
M , I-&O l'rtf i'T-ef f-3-Oi l -9-01 )-10-0 NI-oi M3C\ HVI
3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
13940 13941 13942 13943 13944 13945 13946 13947 13948 13949 13950
b b
D Gb
"P B b
D
P
vn
P fn
P) t > P
n 'P
? V p
P m OO Vp
p. M D -D
T> ' b t > e> p T> p
bP
_
l P
rn O
eL
DP
m bi p
G E. b
DP
rn b
b jd
D
V\ K 6 P p
? P.
1 Pc
D
~ e ' O a m P P f ,
DD
D "b b
m F
m n D e 01 b V
p p no f .
P O DD
b P n P P- b
P rA
(7)C l 'O t Reviewed By:__________________f l )
_ Date:
000014
h i * !_____________
RT 01.14.00 EC2-04b
/ff q iu l
002957
PROTOCOL: 418-020 DOSAGE: 0 (Vehicle) MKD P = Proestrus E = Estrus M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
TYPE OF TEST:
Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
DATE
'tiO l
Hat I <" Ink* M * w
1 2 3 4 5 d 7 8 9 10 11 12 13
Saline Pre-Check 'M i-/ * *
Tech/Time HStT
UW n^>
IlZu / n JSC ant
vm-/ Saline PostCheck Tech/Time lZ06
|P*lL lift
Smears Taken Tech/Time Start
ULmc. ic ^ f
Smears Taken
Time End I2W
Smears Read Vfa'/ Tech/Time Start ivn
)H0 \\SM m J
tl4 3
Smears Read
Time End 12HI iza* ia y f
^6
IJCO n a i t
lia i," .<te fW
w
iOOl IlS ^
|>3
&&
It \\2H <***
____ 1
1
/
Animal Number
13801 13802 13803 13804 13805 13806 13807 13808 13809
p ?r b b
tr D&o '
P6 t> b b p 0
Pz b b D p
h i? p z 0
Vp
Pp D
V f z, V D P
m t/\ T> hP
b?
? f/
m
Pn
r>
fA 0 p
Pp 6
13810
P V p)
13811 13812
t D t> _Cl_ 5 L . D
Reviewed By:
p p
JD
"
D?
De
n
0
Date:
inifwJ-
n jicri'la ju Lt?< ^S (irf^< !J> cJ. "aCtf '// /j,
RT 01.14.00 EC2-04a
000015
EXACT COPY
002958
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020
APFO
Estrous Cycle Evaluation
DOSAGE:
GENERATION: ROUTE:
SPECIES/STRAIN:
0 (Vehicle) MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
DATE
j.lSoi
i n oi m-| l"l`V'<|( l'Z'O'Ol 1-21-*1
12 34 5 6 7 8
Animal Number
T7 9 10 11 12 13
A /
13813 13814 13815 13816 13817 13818 13819 13820 13821 13822 13823 13824 13825 13826 13827
b E f. (fl 0 P
tv\ V
P em
Di e m
D?
pn P 0 P
(r m b E 6
P Yr' m T> P P
l= pn
&ED
m DV E P
& f . rn D P
k ? f r IY D P
P ? L fn D ?
(T P Z rn D E
P(Y \ ) b
hD
Dp
JP E
fO D P
C
O 6 TO rn
p p 6 6 e m t
"7
T /
13828
bp
D PP
13829 13830
> p f P0 6
PDP 0p
Reviewed By:
Date:
000016
RT 01.14.00 EC2-04b /VT
002959
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
AP FO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
1 MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estais
M = Metestrus
D = Diestais DATE
Animal Number 13831 13832 13833 13834 13835 13836 13837 13838 13839 13840 13841 13842 13843 13844 13845 13846 13847 13848 13849
N io l t-ib-S l-r7N m-oi
1234
bP
b P1
JL_
cW
gP
P
b P D
P
rtf
P
p
p
6T ?
P
B
bf P b
N ? ?r
b
p b
b T>
Pb i>
f
0 P f t on
/V) P P S
b?
B P no \>
b Pp e
0 P f, b
p (T) b
HS-oi l-zo-ol W W
y
5 6 7 8 9 10 11 12 13
r
/
DEm O T) e
PB in P r> PD
0b e
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y
/
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if r> T)
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0nn
/
T) D
DPB DD P
T
y
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/
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9e
/
P m/
Reviewed By:
Date:
000017
RT 01.14.00 EC2-04
r x A C T c
ri)
PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
002960
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
Reviewed By:
Date:
000018
RT 01.14.00 EC2-04b
,A/r^W tf y q iu i
jV
PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
002961
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
Reviewed By:
____ Date:
000019
______________ RT 01.14.00 EC2-04b
( exact copy
^lu/o>
PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
002962
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
C ) erjri'i
Jy A^~ 000020
RT 01.14.00 EC2-04b
qiu^od.
002963
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
AP FO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
10MKD
P
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
DATE
,di l-tU-Ol 1-n.oi H8-M
l-Sto-ol f-ai-ot
/ 41 2 3 4 5 6 7 8 9 10 11 12 13
Animal Number
/
13891 13892 13893 13894 13895 13896 13897 13898 13899 13900 13901 13902 13903 13904 13905 13906 13907 13908 13909
T> Z m O
Db f a P
!> P
zD
D o T> E
vn P t
gp
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PB
nP / -O P / p 6/
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/
/
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/
/ /
!
Reviewed By:
Date:
RT 01.14.00 EC2-04
000021
eaACT C O F f \
R iu lo i.
f
PROTOCOL: 418-020 DOSAGE: 10 MKD P = Proestms E = Estais M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE:
APPO GENERATION: P
ROUTE: Orai (Gavage)
002964
t y p e o f TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
ifo)
Reviewed By:______________________________________ Date:______
RT 01.14.00 EC2-04
000022
Q c q lui 03-
002965
PROTOCOL: 418-020 DOSAGE: 30 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Animal Number 13921 13922 13923 13924 13925 13926 13927 13928 13929 13930 13931 13932 13933 13934 13935 13936 13937 13938 13939
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: P Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
l'frol / M 12
llil
34
l-to-ol -aioi 567
8
9
D
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pF p D
P p T D D
P p0
P
PMr f j ) P e
m
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71
10 11 12 13
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/
/
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/ / /
Reviewed By:
Date: . ' g - s p a rs t; (p u '/vO RT 01.14.00 EC2-04b
000023
EXACT COPY
y t qtiWos.
PROTOCOL: 418-020 DOSAGE: 30 MKD P = Proestrus E = Estais
Argus
TEST ARTICLE/SUBSTANCE:
APFO GENERATION: P
ROUTE: Oral (Gavage)
002966
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
000024
01243
ESTROUS CYCLE EVALUATION F1 GENERATION FEMALE RATS
000025
IXC1
Rfni 03l
PROTOCOL: 418-020 DOSAGE: 0 MKD
P = Proestrus E = Estrus M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage)
012432
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
DATE
/--ol sh/*> T O 'hid 5'Pl >'
fiS-*
f-n-o iliaci f'/f-v! 5 ao* -Zhoi
12
4 5 6 7 8 9 10 11 12 13 14
Saline Pre-Check r*PH ff Tech/Time !Z3$ /3>'~ /^ -
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Saline PostCheck Tech/Time
1
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Smears Taken t&l *S3
Tech/Time Start
T"
Smears Taken Time End
r5t>% /33o
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Smears Read ,\*p Y Tech/Time Start i3o U7V
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Time End H trf Hoi, Uro )3M^ 133s" I35& K # 133*7
ivi I3Q 0Y7
Animal Number
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Date:
J r /fio j
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JL .
RT 01.14.00 EC2-04a
o iU
b/A- '%,.. `lik v /o ^
p
01243:
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
F1
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
d./., f/uLt
5Mf-ei iS-' /-/(-61 7'(ll /ir-c S'ib-ti <h
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
n f b c , (Y\ D f
l3> T> D D
\33H T l f r
t?ybS
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/33> T ) D ?
I3 3 S 13 VO
T> : M
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Dp
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P F PP r
C D rxP H
1
@ CC5-i7-ci
Reviewed By:
- -- -_______Date:
l
RT 01.14.00 EC2-04b
000027
EXACT COPY
012434
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
1 MKD
F1
Oral (Gavage)
Rat/Cri:CD (SD) IGS BR VAF/P!us
P = Proestrus
E = Estrus
M = Metestrus
D = Diestms
DATE
sh /o i hki s'/o/; 4 > k S-chA 5ivo 5-iH-oi
>-a-6 ^-n-oi . M
j Hi
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
^Ls^ \ rLb T ?
P5?/ |2 > ? 5
e. D O P " M > e F /n > P
Pi V P
b D ? E Fl M 4 .
T> D f fn O V fc M 0 F
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1r P
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f
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P r b f E _n_ D D
T- -o l
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<><>* Reviewed By:
Fi-
--
Date:
S p /o !
RT 01.14.00 EC2-04b
000028
^ T~C O P Y )
^(u (o-
!
012435
PROTOCOL:
418-020 DOSAGE:
1 MKD
P = Proestrus
E = Estais
M = Metestnjs
D = Diestajs DATE
Animal Number
n
IH Ol IH M
IH07 Hon N ID IH K
ms
NN H l%
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
Sfajo 5/ 7/0/ if'l'i Jt/L
5-iioi F-ifol S V
HTci
5-N-cl $H\
1 2 3 4 5 6 7 8 9 10 11 12 13 14
/?m D ? r
pn D ? A b
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fe
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T> b p er X >
PPb pv X P 6 fh
b p p
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m E
fi
j> C
f
Reviewed By:
Date:
000029
RT 01.14.00 EC2-04b
f- qiu (os-
01243
J
PROTOCOL:
Argus
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE: 3 MKD P = Proestrus
APFO GENERATION: F1
ROUTE: Oral (Gavage)
Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
E = Estais
M = Metestajs D = Diestrus
DATE
Animal Number
m\
\H7> IH3-9, /H 3 0 /4 3 \
IH 3 fe H ' J
m o.
IW U
H 5C W 52 )H S 5 IH 5 L m sE
ljh 5'llt sfr/L 1 234 5
cb
ro D f
CM
D
D P fl
D T) ? 2> V T> E>
rY) b t> 7b D
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DO
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D r (Y]
P /r m 2) Dp
T n PB P ) J7
X
BD
n> b bP Pe r pU-
B
3/U/.I SrW-M 5mW
5-n-ci
S-t'i-ci j i f/Voi
6 7 8 9 10 11 12 13 14
b P e ? fA t> 6 P D D
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G. m 1) A . P B h
Reviewed By:
>.J
Date:
4-
RT 01.14.00 EC2-04b
000030
& X A C T C O P Y "! tlu (os.
01243
PROTOCOL: 418-020 DOSAGE: 3MKD P = Proestrus E = Estais M = Metestrus
Argus
TEST ARTICLE/SUBSTANCE:
APFO GENERATION: F1
ROUTE: Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
DATE
Animal Number
HS3!
...H > l l LlU 'h M fo S IH U 'Z
H 7
-JH 7(e H 7?
m
s/rfoi ? h k imiti f/i'Joi Si?v 3o< 5-I4-6I s-M '/t-el iTD! '/W 5-t-tj S M
21 3 4 5 6 7 8 9 10 11 12 13
P 7? f
D t> jp f
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9 P A fil f T
D T> P E p M
A i />
e n T> E P M D F
D D p e n V E i W6 C
Pf
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if fl'l P D
T) i b b P /n jlF A?
e D V r E0 P
P li P
ce T) V r 6 0 P f D P C T> T> P P O D Y 0 P
M! )
14
M
P D M
i) r i)
D
Reviewed By:
a . Date: RT 01.14.00 EC2-04b
000031
EXACT COPY
^^U tlO u
012438
Argus
PROTOCOL: 418-020 DOSAGE: 10MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Animal Number / m
M ite ms H lo
N IH
m n I50C ,
15oa
I5 5 1507
/5 0 8
1511
1573.
f t iH IS IL
__ 15/7
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE: F1 Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
e lisic i 4,-L f/fiJ n 12 3
<r\&0\ 5M a' 5-4 oi 5-)5-<5'lk-fc!. 5-17-fl* 5 'r tq y-T-vi
3M
4 5 6 7 8 9 10 11 12 13 14
6M r
p > > H
bPP
p
b
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P / ) S T
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P CD
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p
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<2)rvj3rtS--y-o *
Reviewed By:
L tx .
Date:
-5 7 ^ / 0 /
RT 01.14.00 EC2-04b
000032
rt &
012439
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
10MKD
F1
Oral (Gavage)
Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estais
M = Metestrus
D = Diestrus
DATE
Sfa/ot *H/0i slJot //a) -p*t S lil Jli-C 5'iiroi 5-17-CI KO 5-p-l
f/ult)
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
is n D
I5 2 l 152?) 163-1
P
6D T>
150-7 153-% 1531
h
D
D
(5 3 3
D
1631
1537 /5 3 7
r
T) D eD
D T> D ? e D r D T> P D > P \Y\ T>
D P P T? p
Q J>
tA >
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f $ r
D
P P ~^r P J)
000033
^ <71(o>
012440
Argus
PROTOCOL: 418-020 DOSAGE: 30MKD
TEST ARTICLE/SUBSTANCE:
APFO GENERATION: F1
ROUTE: Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
DATE
sfcf*
1
f*A12VTM/i ^L3L\
5-IPW%1li|015-14-cl S'/Irt5-17-c SS4L/?-cf sfuk 4 5 6 7 8 9 10 11 12 13 14
Animal Number
i5 hi )5HH 5H5 HdHo SH9 1550
/55a
1555
T P ~ r Al > g e D
tM
P D Pe
mP t r>
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f
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Pe De
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F. T) P E e D E D E E M
G&lkS-W \
Reviewed By:
Date:
RT 01.14.00 EC2-04b
000034
A A V vwMr
01244
Argus
PROTOCOL:
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION: ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
30 MKD
F1
Oral (Gavage)
Rat/Cri:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus DATE
bh h ti 4 4 1 *(L
S<*l` i - i f f
1 2 3 A5 6 7
5'lh-Di 5\l-b\ K'USC1Ai'h'l sw#
8 9 10 11 12 13 14
Animal Number
/5 ? 7
Th F C b
f
b V Fp
Pb
F
e fi
~D
0 D t> f
T D
9 r\ D b h D p F /J B
l% l
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fb DP
b f) e
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1 "h ? C E P D ? f - D D
i5% 1
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t> -p B
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T) b ? C m 0 P P
b T T P J)
Hoo o
f T> F h 9 P -- D B E b
Reviewed By:
Date:
000035
A
RT 01.14.00 EC2-04b
EXACT COPY
ff
012442
Argus
PROTOCOL: 418-020 DOSAGE:
0 MKD
P = Proestrus E = Estais M = Metestrus D = Destais
Date
Saline Pre-Check Tech/Time
Saline Post-Check Tech/TIme
Smears Taken Tech/Time Start Smears Taken
Time End Smears Read Tech/Time Start Smears Read
Time End
Test Article/Substance:
APFO
GENERATION:
ROUTE:
F1 Oral (Gavage)
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Type of Test: Estrous Cycle Evaluation Species/Strain:
Rat/Crl:CD (SD) IGS BR VAF/Plus
S oi 5M-?/o\ 56
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ANIMAL NUMBER
13 o a I'b D H /3>ip I3 0 S I3 ic
13 / 4 7 3 13 3SM
1^5
1330
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RT 01.14.00 EC1.04a
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000036
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012443
Argus
PROTOCOL: 418-020
Test Article/Substance: APFO
Type of Test: Estrous Cycle Evaluation
DOSAGE:
0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date
GENERATION: F1
ROUTE: Oral (Gavage)
Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus
< 24>& 5-43 0( T ' J ) 5-Z-0 -au-t.' -T 27-4 5-zo 12345 67
ANIMAL NUMBER
31 E M
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Reviewed By:
000037
Date:
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RT 01.14.00 EC1-04b
E.X )T
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012444
Argus
PROTOCOL: 418-020
Test Article/S ubstance: APFO
Type o f Test: Estrous Cycle Evaluation
DOSAGE:
1 . 0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date
GENERATION: F1
ROUTE: Oral (Gavage)
S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus
S-*3-|
12
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ANIMAL NUMBER
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Date: S '/z^ /o (
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RT 01.14.00 EC1-04b
000038
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012445
Argus
PROTOCOL: 418-020
Test Article/S ubstance: APFO
Type o f Test: Estrous Cycle Evaluation
DOSAGE: 1 . 0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date
GENERATION: F1
ROUTE: Oral (Gavage)
S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus
5 fri 1
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ANIMAL NUMBER
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exact copy
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012446
Argus
PROTOCOL: 418-020
Test Article/Substance: APFO
Type o f Test: Estrous Cycle Evaluation
DOSAGE: 3 . 0 MKD
GENERATION: F1
ROUTE: Oral (Gavage)
S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus M = Metestrus D = Diestrus
Date
E'VII s-avoi S M-al S3.S&)
12 3 4
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ANIMAL NUMBER
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D ate: i S / ^ U -------------R T 0 1.14.00 EC1-04b
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Argus
012447
PROTOCOL: 418-020
Test Articie/Sufastance: APFO
Type o f Test: Estrous Cycle Evaluation
DOSAGE:
3 . 0 MKD
P = Proestrus E = Estais M = M etestnjs D = Diestrus
Date
GENERATION:
F1
ROUTE:
Oral (G avage)
S p e c ie s /S tra in :
R at/C rl:C D (S D ) IGS BR V A F /P lu s
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RT 01.14.00 EC1-04b
IbA /A t ^w />
PROTOCOL: 418-020 DOSAGE:
1 0 . 0 MKD
Argus
Test Article/Substance: APFO
GENERATION:
ROUTE:
F1 Oral (Gavage)
P = Proestrus
E = Estrus M = Metestrus D = Diestrus
Date
5-3 oi 12
ANIMAL NUMBER
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012448
Type of Test: Estrous Cycle Evaluation Species/Strain:
Rat/Crl:CD (SD) IGS BR VAF/Plus
5-2A-* 5
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Date: S R T 01.14.00 EC1-04b
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012449
Argus
PROTOCOL: 418-020
Test A rticle/S ubstance: APFO
Type o f Test: Estrous Cycle Evaluation
DOSAGE: 1 0 . 0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date
GENERATION: F1
ROUTE: Oral (Gavage)
S p e c ie s /S tra in : Rat/Crl:CD (SD) IGS BR VAF/Plus
5Vu>[ 5-3.3 0) SM-oi 1 23
<35-01 4
5-^7 S-Z8 oj 567
ANIMAL NUMBER |5 3 3
15117 )5 3 3
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1555
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Date:
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R T 01.14.00 EC1-04b
000043
EXACT COPY
f it ^iulo-
Argus
012450
PROTOCOL: 418-020
Test Articie/Substance: APFO
Type of Test: Estrous Cycle Evaluation
DOSAGE: 3 0 . 0 MKD
GENERATION: F1
ROUTE: Oral (Gavage)
Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus
P = Proestrus
E = Estrus
M = Metestrus D = Diestrus
Date
tu>\ 1
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ANIMAL NUMBER
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R eview ed By:
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D a te : y fz r fiu ,-----------
RT 01.14.00 EC 1-04b
000044
!EXACT COPY 1
P*ih
1
Argus
PROTOCOL: 418-020 DOSAGE:
3 0 . 0 MKD
Test Articie/Substance: APFO
GENERATION:
ROUTE:
F1 Orai (Gavage)
P = Proestrus
E = Estrus M = Metestrus D = Diestrus
Date $'Tu>\ 1
ANIMAL NUMBER (5 3 7 /5 -&
M
b
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012451
Type of Test: Estrous Cycle Evaluation Species/Strain:
Rat/Crl:CD (SD) IGS BR VAF/Plus
S'-ZO-O'I 5'o?l;0/ 5 -3 8 0 1 567
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Reviewed By:
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000045
;i \
Date:
RT 01.14.00 EC1-04