Document vB2x2OLbaL5jzZw7Kz0eNLzrR
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Ho_a_pmA. 19o44
TeJepho(n2e1:5)443-8710
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ARGUS RESEARCH CharlesRiver Laboratories DiscoverayndDevelopmenStervices
September 11, 2002
John Butenhoff, Ph.D., DABT, CIH
o oate 3M Medical Department
3M Center, Building 220-2E-02 St. Paul, Minnesota 55144-1000
Telephone: (651) 733-1962
Telefax:
(651) 733-1773
IF_/_ _ [_ _ _ ['_ _'_
ox [ 2 20ff2 I
RE: Protocol 418-020 Dear Dr. Butenhoff:
Oral (Gavage) Two-Generation (One Litter per Generation) Reproduction Study of Ammonium Perfluorooctanoate (APFO) in Rats
Sponsor's Study Number: T-6889.6
Enclosed are the copies of the estrous cycle evaluation for P and F1 generation rats which you requested.
If you have any questions, please do not hesitate to contact me.
Sincerely,
Ann Frazee, M.S. Study Coordinator
Eric.
00294_
ESTROUS CYCLE EVALUATION P GENERATION FEMALE RATS
ii
"ix
I_EXACTCOPY
i
Oc_q_q-7 _,
PROTOCOL: 418-020
DOSAGE: 0 (Vehicle) MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Argus
TEST ARTICLE/SUBSTANCE:
APFO
GENERATION:
ROUTE:
P
Oral (Gavage)
_TYPEOF TEST: EstrousCycleEvaluation
SPECIES/STRAIN:
Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
I.i-bl i,/,-0(1.3-_1_,'_-01/-_-o_t-_ _-q-oi-_,,L -,_-o,_.,0.01, -11olIIJz_ t'l_'_ :J-_
1
2
3
4
5
6
7
8
9 10 11 12 13 14
.
SaliTneecPhr/eT-iCmheeck 112.3 IIZ_ 11_]5 il7.,o tl_ t1,._... u,t'/ t,'_k _3 I1_'_
113_
Saline PostCheckTech/Time IZ.eo 1155 @.._:_tl"3u I_o_ _tH'l Xl_ _:_ '_ _ 121_ _ _l_ X_=_"_
Smears Taken _J/_=_.._1,*,__.=1,.,
Smears Taken Time End
SmearsRead
fl_ _5_ _ I_51 ,._3,_
_&_,._ o_c U)__ _y_ _._ 3_
Smears Read ..... Time End It._.z_ /LH5 |_q5 _
.d_A
tt'l'_ 11_1t_" "_;q I,_l_1_00_1_ i/.5"_
_t-0_ IzOI I1_'_ i_l "i2_ _ _P_ "_
Animal Number
13801 _ _ "_ F. _ _
13802
"1_ "_ _.. _ _> _
' F__m.. _ _ Z; _ D
E_ _
_'_ I_ _
_)
138o4 C E, _ l'__ _ _ _ _ _' E _ [::, _P ,_
13810 e _,-2_=. _p b _z E b ) F E b D O
'
Review. By:
_, _/'/_._..:
Date:
,'[d'_R/ T 01.14.00 EC2_04a__/
_%_ ,/_/o, _5__'_._- _ _ ,._-.=
_,,-,-0,__
'_,_'".,_,(__"Z"__0,l'_l_, N_'_:_o-_=,,l_-lo,;,_,,_._5_.b,I,_,itoF'0X_A_C,T,,,C._O" PY]:
002948
PROTOCOL: 418-020 DOSAGE: 0 (Vehicle)MKD = = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
AnimalNumber
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE:
P
Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cd:CD_ (SD) IGS BR VAF/Plus(D
I-_-bl I.'_-t_ _-_,Oi ttqlbl _,_.o_l,f_,_ F'7-6( I._,_* 1..01 i.a.el i.i/.ol a'_.ol I-I_rdl H=l-_,x
1
2
34
5
6
7
8
9 10 11 12 13 14
13810
%E
0 _ E r_ _
.-
13817
IV_ _
(3 _ ,_ _ I-_ _,
D
_C_ _) _.._
13820
P
C- _
p -_ /v_ K P _
N i .....
1_28 e C-
,b P ;
_ E. "b b
.i
13829
_
_ "b'
b
1"3 _' /V_ b . P &
N[ b _
...::;
1383o E: b b _' _ 0 D P E ) t'> D ,r_ _
..
c. I-I-t31 Reviewed By:
_
'
'/_, _-"_Z
.. Date:
:_:
I-[f _ I
._
RT 01.14.00 EC2-04b
-
i EXACTCOPY 1 :_
002949
PROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
_
Oral (Garage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
l_l-_ll.;-bl1.5o'l1',1__t._.o_i._( _-_(_-z.o,,._._,1.,.o/,.zl.o,.l,=.6_,, I_,_,
L 1 2
3
4
5
6 ,,,,, 7
8,, 9 10 11 12 13 14
AnimalNumber
......::...
1133883356
"p1_ i(:_::::
'_
,,.
(_.j -
"
11338387.38 ,p _ -3_"L_ _ _ __" _,AA, E_ , _ __..
1_D "_,_...b. _D_
13849
_ "_ _0 '<C , ._
_)
_. .._ J_
Reviewed By: _/ . (_) "_1'1' _
_ ,_ [. _/-oJ
' _.,,-o,
I
Date: /.- [_'.d/
RT 01.14.00 EC2-04b
,
_/t_"_ ' __"_:_e _/"/fEXACT COPY 1.i:
002950
pROTOCOL: 418-020 DOSAGE: 1 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
AnimalNumber
Argus
TEST ARTICLE/SUBSTANCE: APFO GENERATION: ROUTE:
_
Oral (Gavage)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/CrI:C,.D_(SD) IGS BR VAF/Plus_
I
i-_.0.{ =14.-oIi,_l
1
2
3
V_l= i.(,_ _
456
t-P( !_._, _._.6_I._.ol 1.1J_,t-0'_' I_ _,
7 8 9 10 11 12 13 14
......
13854
t'_ .
_ I_
<_
f"
13858 _ _ b "b. b E _0 b b _;_g-"b _b B z,
::
_
5
Reviewed By:
_-!ii
/]1_, _.
Date:
I "! _'.(Y/
RT 01.14.00 EC2-04b
....
002951
,,,
PROTOCOL:
Argus TEST ARTICLE/SUBSTANCE:
:,
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION:
ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
3 MKD
P
= Proestrus
E = Estrus
Oral (Gavage)
R.at/Crl:CD_(SD) IGS BR VAF/Plus_
M = Metestrus D = Diestrus
DATE
B
/--z-c/ i-2-Oi I._0t 123
V,_/_! l.s.ot /_-_1 V3-61 =3.o_ I.'_,
4
5
6
7
8
9
I..= /.It-el i.,;,.=, _-_1 _-_,_.,,_ 10, 11 12 13 14
Animal Number
.....
13866
_ !_ ,,,,,
bE
_
_
P g E ,E_) L._
13871
_b P
13873 E b
_> E
__ 9
C) g _
.,: b _--:E) .i
Reviewed By:
-
Date:
1"lS.d /
,,::_
RT 01.14.00 EC2-O4b
',,=
=
I-EXACTCOPY i "
002952
=ROTOCOL:
Argus
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION:
ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
3 MKD
_
P = Proestrus
E = Estrus
M = Metestrus D = Diestrus
._ Oral .(Gava,ge)
Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
DATE
//'_ l'2'0| /.'_.0| Vqlo_. ,.6,, t4.=_, I-"r,i f,'_._l I'c_'_l I._).oI _I'l.O( i.,z_, 1"/3-oil,-_,,,
1
2
3
4
5
6
7
8
9 10 11 12 13 14
Animal Number
13882
-...... .,138s.
199 b
_'
_n, _) :_ &
_
b
_ _. lj_ ._
r_ _ _ _.. _ O t _ O I) _> 11) _- C)
,,.13887 E _ "b (,_.! e D _ P F_ m "b f __, 3
13889
_38oo
_
_" _ _
__
_ .b _ _--_ _.,..b
_
_) _ _
"_ "_ _._ ,_
F _ F_. _ "p _ ._
,,,,
_
,, ,,,
,,
, ,,
ILl
Reviewed By:
/_ ,_"
Date:
1"(5.(_/ RT 01.14.00 EC2-O4b
_EXACTCOPY Lu/ ...................j..
002953
PROTOCOL:
Argus TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION:
ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
10 MKD
P
P = Proestrus
E = Estrus
M = MetestTus
D = Diestrus
'Oral (Gavage)
Rat/Cd:CD_ (SD! IGS BR VAF/Plus
DATE
j.i-ol i-2-b( I-3-_{ _/qJ61 |,..o1_-/,,-_i1.._ c._.o,' I._._L I-_.ol _.11.1)1i._;L.o, J"l_ I-_,
1
2
3
4
5
6
7
8
9 10 11 12 13 14
Animal Number
138_
13895
-_ t_ _ m _ -P F_...._.. b b E, _, -_ O
-b _ _ m
L_ _) "__....' _'_ b _
_ Cr3 _
_)
13897
L: ,.,_ "_
_) _ _ _) ._._ _' _)
i'_ _
__
1_02 -o _ _. _
139o3 rn "_ _ & 13904 m b _ ;
_ P E m_ _
o h P p b 0 .t_ lb E. _ _
'_ _ F_
_ 8. .,_ i) _ _
or
Reviewed By:
,l_>l,I
/_= _
Date:
/'/',_-t / RT 01.14.00 EC2-04b
002954
PROTOCOL:
Argus
TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
APFO GENERATION:
ROUTE:
Estrous CycleEvaluation SPECIES/STRAIN:
10 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Animal Number
13910 13911 13912
_
Oral (Gavage)
Rat/Cd:CD_ (SD) IGS BR VAF/Plus
_-I-Oit-21'oi(,_o(lY'llo, I._,.olp_,.,_[r_-_i I.t.o_i._.61 I,_._, /./(-0tl_""_=_f_oi l-,,l-_
1
2
34
5
6
7
8
9 10 11 12 13 14
-_ P E _ b b F_. m _ _ _ N_ _ "P Z. D P b F_. b _ L: '% b O g (3 % b L
F _ 0 C) b ) _ _ b ,D I_
113399141_ ..._._. "bb _E,, _ Ie> Pg tP_ _P FL _ D_ gI) Pf _c- Jh
13916 E T_ _ f e 5 P. P g b "b P _-
13919 _ _ P E _ (_ P g b ) _ g _1 D
13920
-'_ b _.
_
P'_ P ___. F__ _
_) _ (__.. _
_
,,
" ''
Reviewed By:
__
_
_
_
Date:
(" t_.#/
!
RT 01.14.00 EC2-04b
.
I-EXACCOTPY
002955
PROTOCOL: 418-020
Argus TEST ARTICLE/SUBSTANCE: ;APFO
ITYPE OF TEST: IEstrous Cycle Evaluation
DOSAGE: :30 MKD
= Proestrus
E = Estrus M = Metestrus D = Diestrus
GENERATION: P
ROUTE: Oral (Gavage) ..
SPECIES/STRAIN: Rat/Cd:CD_ (SD) IGS BR VAF/Plus@
DATE
H-o/ i-_.01 ji._,0_ _/q/b_ ,.S.oJa-/,'=! ii_-m ,._.ot r.'ro, 1.00_, /./i.ot i.,=.o= H_o/ii-Pl_
1
2
3
4
5
6
7
8
9 10 11 12 13 14
_,nimalNumber
13921 -_ _ _ o D P E z> _ _ _ b o P
13923
E_ _
-_ _ E _l_ b
3 _ _
_'_,,, _)
....
13925
13926
E _ "_ ?
_ _1_ r_ _ :_j _Y_ _ _ _
0
"_ _ _
('_ _) p _
_
_) _P _" _ _ .'_
13927
-r_ _
i_
L_ p
_
m
_) _
_ _ "_ _
13930
"_ _ _
_'_ _) P ..._ "_
__
_ r_ _
.._
13932 _ _ P E. _ _ b E. _ b 3) E ,_ _
13935
_" (_ _
#
_P
F_ %
bZ
_, m-_)
0
':i.
13936 E _ "b o _ h P _ 'b P b _ 0
13937 'Z) "_ e Z, b p p ;. :b -_ "_ ;. o b
..
_(_)])P I.It.ot
,-:
RT01.14.E0C02_b
' EXACTCOPY_.
002956
,
PROTOCOL:
Argus :
.........
TEST ARTICLE/SUBSTANCE:
,.,.
TYPE OF TEST:
418-020 ,=,,
DOSAGE:
APFO ,, GENERATION:
..........
IROUTE:
IEstrous Cycle Evaluation SPECIES/STRAIN:
30 MKD
.. , P :
P = Proestrus
E = Estrus
M -- Metestrus
D = Diestrus
Oral (Garage)
,
, ,,
Rat/Cd:CD_ (SD) IGS BR VAF/Plus
, ,,,
,
m,,,
.,.
DATE
Animal Number
13_9
t./-o/ _i-_.-ol _-_01 Y'f/ol I._.o, t-_'#( i'_ot
1
2
3
4
5
6
7
E 'b "b ib E "fq _
_'__. I,.o_ i.,o-m I.It.ot /.!_._.. H_( Hq.o, 8 9 10 11 12 13 14
"_ ? ? _ m -O
::.... _3_945 -_-o c#- E mb _O1).p _ Lrq. 0b ?, E_, , rzn::>D-_ #
_o ...=., t:::, b : P E _ I::', E_. _ _, "b P' f_._f'4
,_
,,,,
G@_.. _-5.o_
Reviewed By:
'_ , __"
::, =.
Date:
[-!,._'.(_/ RT 01.14.00 EC2-04b
002957
3ROTOCOL: 418-020
DOSAGE: ',0(Vehicle) MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
Tech/Time
Argus TEST ARTII_LE./SUBSTANCE:
APFO
GENERATION:
' I_OUTE:
... =
.... Oral(Gavage) .........
,,t<S.olm(,,,,I H?-o, !-4-'| /;/_,_, II1_1*,_//01
12 34 s _z 8
It ;3:)s_
V..c _
:7_ ds_ _./_..
TYPEOF TEST: EstrousCycleEvaluation
!SPECIES/STRAIN: Ra..t/Cd:CD_(SD) IGS BR VAF/Plus_
/
/ 9 lO 11 12 13 1,4 I
CheckTech/TimeiZ06 lit{?_. |_5"_, 1_0 I1_"_ "J_
....
I
Saline Post- _L,/ '_ Y-._'tL _
IL_Ic I_'_(_!'_
/
Tech/"l'imeStart li_, ?_lh_P'rT'"_"
J_'/P_
"SmearsTaken
'/
: -_. TeSchm/TimeeaRrSsetarat d'IvZo_l ( _3 I1_'_ _ '_12,01 _I_'_--'t- __I,'L_ __. ;_'_
'
,
Time End I_'_ l/lvO tl_Lt |l_q _ _ IL_(Q IL_
/
";
Smears Read'
"
_$
" I'
Time End _2_ I?__.C_I_0_ ji_'_t 1_'_3
I"b3i'e
i
ii
_
Animal Number P
_803....... O E b b D E _:
13804
_'_ '_7 {9 .,_ _-)
,,
/
"
'"
"
13807
E (YI b _) E , ._. _).
_8_o _-- _ t_
Reviewed By:
,--) 5
__
D.,. E
b0
_
r_ t_ /_
e;D /
Date:
(_ A_;n'_ _ _r/_zumd,_/_'_J.
_ 'h,t/a/
"_: !_
RT01.14.00EC2-04a
;'i_
::;
....
..
002958
PROTOCOL:
418-020 DOSAGE:
Argus
:
,
TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
=,
ITYPE OF TEST:
Estrous Cycle Evaluation SPECIES/STRAIN:
0 (Vehicle).MKD
P
P = Proestrus
E = Estrus
M = Metestrus D = Diestrus
Oral (Gavage).
Rat/Cd:CD@(SD) IGS B..RVAF/Plus@
'DATE ,,, 1,1.%1I-J6ol I.iT.o/ 1.0'_._ I-I_q I.z,a.oI !-Zl,._e
/
1
2
3
4
5
6
7
8
9
Animal Number
13813 i_ _ _ _ o P _ 13814 _ D _ ,o E ,_ ,O
13815 _" '_ m V_ D _p E
13816 P _. 011 _ _ ?
13817 e" _ rn b, E 6 .m
13818 P 21 01 "b P a m
_,,_9 _ m-p y_.,E. _ D .......
10 11 12 13 /4 /
/ /
/
/,,,
/
/
13821
h
D F_ _'_ D
p
e
/
13822 13823
_ 'J_
P_ p_
}_ D p _'_ D ;_
"L_
7/
13824
_'- _
_
_
O6
_
/
/ 1382_ _ _ b b _ _ m /
13826
_ _ _ _,, D p
_,
13827
b
_- _
_ J_ p
I_
13828
/1_ b
?_
PD
P
/
13829
I%j b
P _J D D P
/
13830
b
_) 6
b
PP
6/
'"
't
J'
.,,
,,
,.,
,:
Da,e. RT 01.14.00 EC2-O4b
002959
PROTOCOL: 418-020 DOSAGE: 1 MKD
= Proestrus E = Estrus M = Metestrus D = Diestrus
Argus
TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
_
Oral (Gavage)
DATE AnimalNumber
1'15.oit._,._, t.m._ i_.o,
1
2
3
4
I-_-_ !-=,_1 t._I
5
6
7
13831
13832
13833
_
_
b_
_." "_
"_ "_2
E_ _
_
p
O E rI")
o_ e
L-" r13 !E)
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Crt:CD_ (SD) IGS BR VAF/Plus
/,//
8 9 10 11 12 13
//
".......
13835
t_"_ _
_) p E
_'_.
'
1133883634 c-- .m -_ P E E) E)
/
13838 13837
113383_9o
O f _
b
_ -T_ p _
NE bP _) _
0 O9 P _ _:
LOr _b _E)
..... /
13843 b (2 E. _ o p g
t
138_.5 r_vl _ pf g_- o _) pp
/
:-.-
13846
L_-_" _, ri_ b
0e6
/
+.
13848 ,0 9 g. h o e /
13849
P
,_f_.... m
b
f'ft /
i
RT 01.14.00 EC2-O4b
=
,:_EXACT_"O_OJ',,v' _._..- qkilo _- ........ : _.' ....... : ........
002960
PROTOCOL:
_18-020
i=
'DOSAGE:
1 MKD = Proestrus
E = Estrus
M = Metestrus D = Diestrus
DATE
,
,.
Animal Number
13850 13851
13852
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
P
Oral (Gavage)
'
"I'
I-I_ol, j.,_,_j _.61 I.,t ._ I-_.oI-_t=.ol (-_IPoI!
1
2
3
4
5
6
7
8
.,
_ _ V C '_ r) __ _b _ i'n b o _ e,
_
['_ _
_
D_
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN:
Rat/Cd:CD_) (SD) IGS BR VAF/Plus_)
/t
9
10 11 12 13 /14
/
/
/
13853
'_--,--13855 13856
44 t::) P
_ -_ P _ _4 D p _
D_ p
OD P O D iP
/ ./
_r
/
13857
_
"_
_
WI
_, _"
/
13858 _ 1;) _) E- 0 b D
/
1385_ P F_.._4 b P ,_ _ /
13860
I'_
_
_,_ _1_ O P
_ /"
/
,,
,,,
, ,,,
,i
/
/
/
,,,
/
.../
, ....
_
,,,
,,,
_ __ i,,, u
_
Reviewed By:
Date: ..
> .i/-
RT 01.14.00 EC2-04b
.... '
_ ',F, _'
t
l;__u_
...j;
002961
PROTOCOL: 418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE
!Animal Number
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION: P
ROUTE: Oral (Gavage)
TYPE OF TEST:
iEstrous Cycle Evaluation SPECIES/STRAIN: IRat/CrhCD_ (SD) IGS BR VAF/Plus_
1.13_.0I.1,_,.m I._/.ai -,t_' 1234
1-1'1-_I-Zo_l I-_11_1
56
7
8
// 9 10 11 12 13 1 4
/
138612 b _P g_- b oo _pp ep
/
13863
_
_
I-_
_2 _
_)
_)
/"
-. 13862 _q _ P F. D _ p
13868
_
f
_
b
O
p
Z
1133886679
_1_ _"E) _CL_ mb
DO b
e_"
/
1,33887710 I/3---T_b 3fP' __'. EP" D_ PD
/
-:
113387837.
13876 138n
_
.4 b (vl _
__ f. OO _ P_,
_ f'. o _ p P f. e- _ n
13879
I_
b _1
Db
/_
/
jf /
Reviewed By:
Date:
.;
-: i!.
- :_ , ...y: ' }:i
/ RT 01.14.00 EC2-O4b
I- XACcTOPY[
002962
PROTOCOL:
418-020 DOSAGE: 3 MKD P = Proestrus E = Estrus M = Metesl_JS D = Diestrus
DATE
Animal Number
13880
Argus
,m
TEST ARTICLE/SUBSTANCE:
APFO !GENERATION:
P
ROUTE: Oral (Gavage)
I.t_'_1 I.l,_l t.(I.O# l,il-_t I-Pi-o I-zo_ lill.=l
1
2
3
4
5
6
7
!._... _ P _ _ _ p
TYPE OF TEST:
Estrous CYCle Evaluation SPECIES/STRAIN: Rat/Cd:Cl_i) (SD) IGS BR VAF/Plus_
/
8
9 10 11 12 13 /14
/
/
13883,,, rfl 0 _ _ 0 b _
f a,_
" " 13885 _ m _ E. _-",.e, 6 13886 E _- 171E- _ _ _
,
/
/
/
/
13887
_
P_
b0
9_
/
:.
13888
D .... O. i-_") ,__... 0 _ p
Z/
:"
/
/
)1131 l-i_-='i
e_
j,,,,,/'==.
J_
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RT01.14.00 EC2-04b
._, :i
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_'-E-_ACCTOPY :
002963
PROTOCOL:
418-020 DOSAGE: 10 MKD P = Proestrus E = Estrus " M = Metestrus D = Diestrus
DATE
AnimalNumber
13891
13892
Argus TEST ARTICLFJSUBSTANCE:
APFO
.....
GENERATION: ROUTE:
_
Oral (Gavage)
I'l_:d I-Ila,o=Hq.OI !1,111..6..1PR-' _o_1 I-,11-_1]
12
34
5
6
7 ...8.
,3 D _
b T_ _
r_ o
_
.D
D ..._
p
_
TYPE OF TEST:
Estrous Cycle .Evaluation SPECIES/STRAIN: Rat/Cd:CD_ (SD)IGS BR VAF/Plus
9 10 11
.... ,
?/
12 13
/
/
/
'
13895
,/v__ i_ ._ _ _'_ I_1 _)
-- 13896 lE _ _X> E 1> tb
138_ _1 t> P Y__o. D ?
13899 P 3 h _ o d O
13..991 _ E. iXl _ 0 P e
/
/
/
/
13903
_3_
13995
... 13906
13997
IP
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/3 5 _. _P F' o o,
_ I) T) P E .6 _b
1#
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_ 1/
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...
_' _:i
Reviewed By:
_
Date:
'_:
RT 01.14.00 EC2-04b
002964
PROTOCOl:
Argus
TEST ARTICL_SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
10 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
APFO GENERATION:
=
ROUTE: Oral (Gavage)
!Estrous, Cycle Evaluation SPECIES/STRAIN:
Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
DATE
_)i_,-,_
1
2
!.rl.01,1.ol i-_=
34
5
i.zool 1-31-el
6
7
8
"/ 9 10 11 12 13 / /14
Animal Number
13910 13911 13912
_ "b _ ,ITI _ D D _ _ B _ o 1_ 13
_I -_ _ _ E D i)
/
.,/ /
/
13913
_" _- ('_ b
O _ ]_
/
.... 139126 _b f__.. N_ _b oP p_ _em 139178 __ b(_ _- ',bb _o _p P_,
/ /
13919
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ReviewedBy:
Date:
i,
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'_ RT 01.14.00 EC2-04b
;._._--!_,_-..--__-:-:-->._,.-_
002965
PROTOCOL:
418-020 DOSAGE:
30 MKD ....... P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
P
Oral (Gavage)
TYPE OF TEST: tEstmus Cycle Evaluation SPECIES/STRAIN: Rat/Cd:CD(D(SD) IGS BR VAF/Plus_
DATE
1.1";,0]1l,l,e! il-r/.OI I._._1 |-Ppot I-zo.=111-31.o
.,
1
2
3
4
5
6 ,, 7
8
9
Animal Number
13921 13922 13923
...... _ _ _ "_ .__ -_
D
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T') _ E" _) _:)
_ .__,,, O _
13924
_
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_
D
E, P
13926 13927
_ mb
0 E" D '_
_ "_ "_ _ E" _) =p
13928 13929
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L_. _"
_
E, {Vl _ _: .
,.
13930
t_
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p
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13931
_
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13932 P _ b o b,
13933 t_ .-_ ?__ nl c, _ .,,_
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10 11 12 13
//
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/
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/ 13935
_
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13936
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13937
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13939
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P L--" D n
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RTo1.14E.oCo2-_,
002966
,
:
PROTOCOL:
418-020. DOSAGE:
30 MKD P = ProestnJs E = Estrus
Argus .,
TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
_
... ROUTE:
Oral (Gavage)
,
TYPE OF TEST:
Estrous Cycle Evaluation ISPECiES/STRAIN: Rat/Crt:CD_ (SD) IGS BR VAF/Plus_)
M = Metestrus D = Diestrus
DATE
.,o
I1_-01 i.,_,'__..,_.o,.,_.o,i._-ol,,z,,oI_-'_ b 1 z 3 4 5 e 7_ _s._, 9 lo
// 11 12 13 A4
Anim1a3l N9um4b0er 6 F/ _ D P _, _ 1394_2. _m'I -_P _ __, oo __b ?P
.... ._.._
1_3.9343_ __- "m_ "-__ _fj> E0 ,,,m_ ,_ _._ 13943 d t4 _ "b e m n
.... / /
/
/
133994487 1P3 E_, P_ q Ib-) _o Ip_ _: /
13950
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Reviewed By:
%_
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RT 01.14.00 EC24)4b
,I,/ol Date: ,/_._
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I EAoOOfP,,q
012431
ESTROUS CYCLE EVALUATION F1 GENERATION FEMALE RATS
PROTOCOL:
418-020 DOSAGE: 0 MKD P = Proestrus E = Estms M = Metestrus D = Diesltus
DATE"
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
F1
ROUTE: Oral (Gavage)
012432
TYPE OF TEST: Estrous Cycle Evaluation SPECiES/STRAIN: Rat/Cd:Cl_b (SD) IGS BR VAF/Plus_
J
_-z-ol 4/_, _/_j _t_t :_'l_'O_15Lz"_i_-_,I-- _;s-al S'-M-e__-n-_l _J_0t F-_J __o_ _--_i
1 /2 " 3 4
5
67
8
9 10 11 12 13 14
Saline Pre-Check _'P" _ TecW13me /23S ,_
_ (}o '(_
_/.t= _
_ ._C _
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_"_-"_ NIICF _)
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CheckTech/Time
Smears Taken _% SmearsRead ,uP,, SmearsRead
lifO0 t3o_
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1" b
iVt_ (I_ .4u_f' bc D ,Z.ET:'._%__=I_._%, /,3(.// _fz_
Animal Number
_2_'<,_/=_
FS/o .ffl _ f', E b P ? E b
ReviewedBy: /' LI
Date:
_;-/z. _//0 t
l
V'
@(_ V ,r/J,o]}
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RT 01.14.01:) EC2-O4a
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012433
Argus
pRoO:CrOL_ : " :T"ES'T " " ' ARTICLE/SUBSTANCE: "
"TY'PE O"F TES.T.:..
418-J0, 2i 0 DOSAGE:
,, [APFO GENERATION: ROUTE:
,,, EstrousCycle Evaluation
....
:SPECIES/STRAiN:
0 MKD
F1
Oral (Gavage)
Rat/Cd:CD_ (SD) IGS BR VAF/Ptus_
P = Proestrus
E = Estms
M = Metestms
D = Oiestrus
.....O. ATE_t,/o_,17_1'/_,.,/.,,X_,_ _"_s',,.o_,-,_5.-,,__-.,7, -_0._. ,._,,.,__.,_L.,I,
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Anima.,.l Number
@
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/33& _ t> i' _- p o ? c p4 b /_ E /'ft. 'D
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/350 e ,_ _, _ .,,,_ b "
nO:_ P f'
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13,55 r4 D /_ e" "p o _. _ .... 1_ J_ _ E T'_ D
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,,
RT 01,14.00 EC2-04b
_)
:
PROTOCOL:
418-020 DOSAGE:
1 MKD P = Proestrus E = Estrus
M = Metesb'us D Diestrus
Argus TEST ARTICLEISUBSTANCE:
APFO !GENERATION:
ROUTE:
F1
Oral (Gavage),
,,
1
2
34
5
6
7
AnimalNumber
012434
TYPE OF TEST: Estrous Cycle Evaluation SPECIES/STRAIN: Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
..
8 9 10 11 12 13 14
152'7
J'bgl
I'bggl%$b
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I--RT
/ 01.14.00 EO2-04b
,_
,
PROTOCOL:
418-020 DOSAGE:
1 MKD
P = Proestrus
E = Estrus
M = Metestrus
D = Diestrus
012435
Argus
"
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,
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TEST ARTICLE/SUBSTANCE:
TYPEOF TEST:
,,
,_
APFO ,GENERATION: ROUTE:
EstrousCycleEva,l. uationn SPECIES/STRAIN:
F1
Oral(Gavage)
Rat/Cd:CD(_S)D)IGSBRVAF/Plus@
1 2 3 4 5 6 7 8 9 10 11 12 13 14
, ,,
,,,, ,
Animal Number
I,,40,'?_ _ e,,_<'-b D P ,,_ b_ D D E b D
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lqlZ e _ D F,..E.. o ) u g b _0 'P E D I_!5 _ E m _,b P _ b b E _ E n_ _ Iqlk -P c D _ P d g _ p _ _. m g C
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-"-,_,
/ RT/ 01.1" 4,00EC2-04b
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012436
j PROTOCOL:
Argus TEST ARTICLE/SUBSTANCE:
TYPE OF TEST:
418-020 DOSAGE:
IAPFO GENERATION:
ROUTE:
Estrous Cycle Evaluation SPECIES/STRAIN:
3 MKD
F1
t '_L
P = Proestrus
Oral (Garage)
.,.,
Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
i
,
E = Esirus
M = Metestrus
D = Diestrus
'_
_/./o,';d/4/,_t,_o,,/'.,_,__o.,_r,._.._,-,_s,-ro.!,,-,_,._d, ;'/.,
1
2
3 45
6. 7 8 9 10, 11 12 13 14
AnimalNumber
D,
f _ t4 _
,,z_
, /42H,, _ _ _ .r..--
E
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r
lqS-_ "-O _C ,__ _ ]) E _ . UP ff i_
ReviewedBy:.
,j.
Date:
,
./
O(./
RT 01.14.00 EC2-04b
_AO_ 'OPV:I
012437
j
,,
.... ,
PROTOCOL:
418-020 DOSAGE:
3 MKD -P = Proestrus
E = Estrus
M = Metestrus D = Diestrus
,,_
,.
i
,,,,, ,
Argus
*TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
F1
Oral (Gavage)
,
.....
.,,
TYPE OF TEST:
Estrous Cycle Evaluation SPECIES/STRAIN:
Rat/Cd:CD@(SD) IGS BR VAF/Ptus@
,.'.. :
,
,,
1
2
3
4
5 6 .... 7
89
10 11 12 13 14
Animal Number
,,
)'-!74 I/-/;)2
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s .r)_ 9. 5 O _
_- _5, .J_ t M b ? o E _ [.)_ ,_ E o
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ReviewedBy: i__._
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Date:
, %/:2_//o( RT 01.14.00 EC2-04b
012438
_) ...... PROTOCOL:
418-020 DOSAGE:
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION:
ROUTE:
TYPE OF TEST:
EstrousCycle Evaluation _SPECIES/STRAIN:
110MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
_,_
AnimalNumber
F1
Oral (Gavage)
Rat/CrI:CD@(SD) IGS BR VAF/Plus_
g,/o4.!.._/_. i/._. ' _,.',""_o,,',__-'_5-,=s.,_,:._r._, _,
1
2
3
4
56
7
8
9 10 11 12 ! 3 14
/qTq -_ _ e p e a .o e
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147) 15o0
/for I_135 1507
s _ D P 7> ,,,a,, "_ $ E N ID P. _ D _ d E D b f g 0 b P _E B D
_ D __ p _ _ o g e 12_D
D
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e- D D P ff D b E 6 _ 19 'P g
15,1 _ ,_ _ _ "b ? _ a _ E ,__ .D P
1.5i& e D .,_ e p.. o P
p
DE o
C_O_r,,,..rp__- #'-o,
ReviewedBy: __-_j
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Date:
.5"/z.-,_/0 ( RT 01.14.00 EC2-04b
O12439
PROTOCOL:
418-020 DOSAGE:
Argus ITEST ARTICLE/SUBSTANCE:
APFO
, ,i
,,,
GENERATION: ROUTE:
TYPE OF TEST:
EstrousCycle Evaluation SPECIES/STRAIN:
10 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
DATE ..
, F,,r:1
Oral (Gava.ge)
IRat/Crl.'CD_(SD) IGS BR VAF/Plus_
5//!/5o",/=//Q_i/',,oZ_/,'., _1,'1S0_0_','O5J'=0_.*0_''_ S'=_, _/J0. 1 '2 3 4 5 6 7 8 9 10 11 12 13 14
Animal Number
15_3 _ JSP-P. e
D D _ E _" _ _ ,,i o _ _ d _ D
_M
P
N
l_ P F-_ _ nt ._
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_,k." H 'L.._xW_'IF '! :
PROTOCOL:
418-020 DOSAGE:
30 MKD .... P = Proestrus E = Estrus M = Metesb_JS D = Diestrus
DATE
Argus TEST ARTICLE/SUBSTANCE:
APFO GENERATION: ROUTE:
-, F1
Oral(Gavage)
012440
!TYPE OF TEST: 'EstrousCycle Evaluation SPECIES/STRAIN: Rat/Cd:CD_()SD) IGSBRVAF/Plus@
T.#1/5.19.Ol
U(J
RT 01.14.00EC2-04b
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01244j
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PROTOCOL:
Argus TEST ARTICLE/SUBSTANCE:
., TYPE OF TEST:
418-020 DOSAGE:
A,,PF..O..... GENERATION: ROUTE:
Est.rousCycle Eva,!uation SPECIES/STRAIN:
30 MKD.
F1
P = Proestrus
E = Estrus
Oral (Gavage)
, RaUCd:CD@ (SD) IGS BR VAF/Plus@
M = Metestrus D = Diestrus
DATE
Animal Number
15P_
_J_(/P' g'k_
1
2
__
_;_/_,1_'f,/o, g-ia_i..sI,,]o,]6'_-'
3
4
5
6
7
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8
9
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f/za_i 14
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p g _ ,3 > g > so p E/"_ E .b C
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RT 01.14.00 EC2-O4b
|
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O12443
'PROTOCOL: _ 418-020 DOSAGE:
0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus Test Article/Substance: .....
APFO GENERATION: ROUTE:
F1
Oral (Gavage)
Date
Salin'e Pre-_heck Tech/Time
_0i 1
_0 I_.
5_-I?2'1
_ 1_ 3 _
s'_q'_3l
_ _,23 _
W'_"4l
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'Saline Post-Check _
_
'I =_ .... _
Type of Test: EstrousCycle Evaluation Species/Strain:
Rat/CrI:CVDA_F/P(lSusD_) IGS BR
_?-_5'_15A,'_/6, 6
T'z,_r _ 0 7.4
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1150
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Tech/Time Start
_.#Z ""_-
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l_,_,
13_
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Smears Read
I tE'_
Time End ANIMAL NUMBER
/_1 ii
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ii
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ii
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RT 01.14.00 EC1.04a
012443
PROTOCOL: 418-020
DOSAGE:
0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus Test Article/Substance:
APFO GENERATION: ROUTE:
F1
!Oral(Gavage)
Type of Test: EstrousCycle Evaluation
Species/Strain: Rat/Cd:Cl:_ (SD) IGS BR VAF/Plus_
Date
ANIMAL NUMBER
__L.%31
._._/._b_ 1
_
5"-_.ol 2
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_,_'-/.o/ 3
P
5-2_'.0/_;-0,.,-.,.
4
5
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Oa,eRT 01,14.00 EC1-04b
PROTOCOL:
418-020
!DOSAGE:
1.0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus
,,-'
Test Article/Substance:
APFO
GENERATION:
ROUTE:
F1
Oral (Gavage)
O12444
Type of Test:
EstrousCycleEvaluation
Species/Strain: Rat/CrI:CD_ (SD) IGS BR VAF/PIus@
Date
....
ANIMAL NUMBER
13_
)_b_
__,z.'_i=t 5._3.ot
1
2
L
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D p. E
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RT 01.14.00 EC1-04b
... _;_ _lul_.
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PROTOCOL: 418-020 DOSAGE:
Argus
Test'Article/Substance: APFO
GENERATION:
ROUTE:
1.0 MKD F1 P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date ANIMAL NUMBER
5z_t 1
Oral (Gavage)
5.,_%.of 2
_.;tL/'os 3
5".Jf.d/ 4
' 012445
Type of Test: Estrous Cycle Evaluation :Species/Strain:
Rat/CrI:CD (SD) IGS BR VAF/Plus
-:._-_) _._.2,.'_.oI ._.,_5._ !
5
6
7
I_c,7 ;flip
p r_.. f_ D _ t4 D b ... _ ,,
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Reviewed By:
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Date: _--/,_P//_a / RT 01.14.00 EC1-04b
EXACT COPY i
0124.46
,.. ==
PROTOCOL: 18-020
Argus
....
.
Test Article/Substance:
APFO
Type of Test: Estrous Cycle Evaluation
DOSAGE:
3.0 MKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
GENERATION: FI
ROUTE: Oral (Gavage)
Species/Strain:
Rat/Cd:CD@(SD) IGS BR VAF/Plus
Date
j_.Z_ 1
b'-;_%-ot 5.-_'o)
2
3
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ANIMAL NUMBER
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Reviewed By: ..___--=o-_I ._.' __L.d_
Date: R,T_40[1,/.Z1'44A."0_0 /EC1-04b
., 0PY
PROTOCOL: 418-020 DOSAGE:
3.0 HKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
Date
ANIMAL NUMBER
I_(_3
Arg_
Test Article/Substance: APFO
GENERATION:
ROUTE:
El
Oral (Gavage)
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012447
Type of Test: Estrous Cycle Evaluation
Species/Strain: Rat/CrI:CD_ (SD) IGS BR VAF/Ptus
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Date: ,_,_"/2.t.'*/ RT 01.14.00 ECI-O4b
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_ROTOCOL: 418-020 DOSAGE:
10.0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus
Test Article/Substance: APFO
'GENERATION:
'RouTE:
F1
LOral(Gavage)
012448
Type of Test: Estrous Cycle Evaluation Species/Strain:
Rat/CrI:CD@(SD) IGS BR VAF/Plus
Date
ANIMAL NUMBER
P/%_ /_._b
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5.,23.01 2
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RT 01.14.00 ECl-04b
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012449
PROTOCOL: 418-020 DOSAGE:
Argus
Test Article/Substance: APFO
GENERATION:
ROUTE:
10.0 MKD
F1
= Proestrus E = Estrus M = Metestrus D = Diestrus
Date
_ 1
ANIMAL NUMBER
Oral (Gavage)
E._3,0) 2
5.;_LI'ol 3
_.a_.ot 4
Type of Test: Estrous Cycle Evaluation
Species/Strain: Rat/Crl:CD (SD) IGS BR VAF/Plus
5"'z_'_I 5
5.9,7.oi 6
_k':ZB-O# 7
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Date: ,.,_/,_../f# / RT 01.14.00 EC1-04b
E_ACTC0IPY
PROTOCOL: 418-020
Argus Test Article/Substance:
APFO
O12430
Type of Test: Estrous Cycle Evaluation
DOSAGE:
30.0 HKD P = Proestrus E = Estrus M = Metestrus D = Diestrus
GENERATION: F1
ROUTE: Oral (Gavage)
Species/Strain:
Rat/Cd:CD_ (SD) IGS BR VAF/Plus_
Date
_ 1
ANIMAL NUMBER
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2
3
4
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5
6
7
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RT 01.14.00ECI-O4b
_om _
PROTOCOL.: 418-020 DOSAGE:
30.0 MKD
P = Proestrus E = Estrus M = Metestrus D = Diestrus
Argus
Test Article/Substance: APFO
GENERATION: ROUTE:
F1
Oral (Gavage)
.-
i_,m
- 012451
Type of Test: Estrous Cycle Evaluation Species/Strain:
Rat/CrI:VCADF_/P(lSuDs) IGS BR ii
1
2
3
4
5
6
7
ANIMAL NUMBER
J5% b _ m D P e
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p _ m D D eN
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RT 01,14.00 EC1-04b
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